RESPONSE OF THE JOINT ETHICO-MEDICAL COMMITTEE OF THE GUILD OF
AND THE CATHOLIC UNION OF GREAT BRITAIN
HUMAN TISSUE AND EMBRYOS (DRAFT) BILL
The Joint Ethico-Medical Committee is comprised of Members of the Guild of Catholic Doctors and the Catholic Union of the United Kingdom. The Guild of Catholic Doctors represents Catholic Medical Practitioners. The Catholic Union is an organization of the Catholic laity which represents the Catholic viewpoint, where relevant, in Parliamentary and legislative matters.
We are opposed to the creation of human embryos, including cloned embryos and ‘cybrids’ for the purposes of destructive research and training There is no good scientific evidence to suggest that ‘cybrids’ are either satisfactory models for human disease or suitable sources of viable stem cells. Indeed, there is persuasive evidence to the contrary.It is misleading to suggest that embryo research is of any immediate therapeutic use in human disease. There have been no actual therapeutic gains from the use of embryonic stem cells. However, adult stem cells have been used successfully in clinical practice for years, the best example being bone marrow transplantation. Adult stem cell therapy does not raise serious ethical problems and overcomes the problems of immunological rejection. Adult stem cell research should be encouraged and financed.Respect for life requires that science and technology should always be at the service of man and his integral development. Society as a whole must respect, defend and promote the dignity of every human person, at every moment and in every condition of that person's life.
- The proposed Bill introduces major changes in relation to reproductive technology, embryo research, surrogacy arrangements and the meaning of parenthood in relation to assisted reproduction. It will create a new body, the Regulatory Authority for Tissues and Embryos (RATE) to replace the Human Embryology and Fertilization Authority (HEFA) and the Human Tissues Authority. RATE will have widespread jurisdiction over the use of cadavers, human tissues, and live organs for transplantation, blood, gametes and embryos. The draft Bill will permit destructive embryo research for an extended range of research including basic scientific research and also allow the creation of embryos for training in reproductive technology.
- We welcome the opportunity to comment on this complex piece of legislation. However, we contend that adult stem cell therapy using cell lines derived from adult stem cells or umbilical cord cells rather than embryonic stem cells, is already of proven therapeutic benefit whilst posing fewer, if any, serious ethical dilemmas. We are not aware of any examples of where embryonic stem cells have been shown to be of therapeutic benefit in human disease. Indeed, Lord Winston has stated that “I am not entirely convinced that embryonic stem cells will, in my lifetime, and possibly anybody’s lifetime for that matter, be holding quite the promise that we desperately hope they will”.
- “From the time that the ovum is fertilized, a life is begun which is neither that of the father nor the mother; it is rather the life of a new human being with his own growth. It would never be made human if it were not human already. This has always been clear, and modern genetic science offers clear confirmation. It has demonstrated that from the first instant there is established the programme of what this living being will be: a person, this individual person with his characteristic aspects already well determined. Right from fertilization the adventure of a human life begins, and each of its capacities requires time-a rather lengthy time-to find its place and to be in a position to act". Science is able to demonstrate that the human embryo is a genetically unique individual with a personal presence from the time that life first begins. “How could a human individual not be a human person?”. From a moral standpoint we agree with the famous dictum of Tertullian. “He who will one day be a man is a man already".
- Human beings can now be created in ways other than natural conception: for example, by in vitro fertilization, embryo splitting or cell nuclear transfer—including, perhaps, the use of a non-human ovum. It may be uncertain whether such techniques will always result in a living human embryo. Nevertheless, any doubts regarding the ethical status of interspecies and ‘cybrid’ embryos and chimaeras serve to reinforce the view that embryos produced in vitro through IVF and cloning are indeed fully human. The draft Bill recognizes that a live human embryo includes an egg that is in process of fertilization or is undergoing any other process capable of resulting in an embryo.
- Our concerns about the draft Embryos Bill relate to the
- The production (and destruction) of human embryos outside the body,
- Respect for the meaning and value of human procreation and
- The need and role of parents.
- We are opposed to any research that involves a fatal outcome on a human subject at whatever stage of development and whether or not it may have therapeutic benefit for others.
- “Human life must be respected and protected absolutely from the moment of conception. From the first moment of his existence, a human being must be recognized as having the rights of a person – among which is the inviolable right of every innocent being to life.” The inalienable right to life of every innocent human individual is a constitutive element of a civil society and its legislation. Every human being has a right to life and physical integrity from the moment of conception until natural death. This right is not a concession of the State nor conferred by the parents but is inherent and inalienable by virtue of the creative act which gave rise to the individual.
- Respect for life requires that science and technology should always be at the service of man and his integral development. Society as a whole must respect, defend and promote the dignity of every human person, at every moment and in every condition of that person's life.
- "The future of humanity passes by way of the family". The fundamental task of the family is to serve life and to transmit though procreation the divine image from person to person. The love of husband and wife involves a participation in the mystery of life and a share in the love of God Himself. The Catholic Church teaches that human procreation must therefore remain within the context of marriage. The generation of new human life must therefore be a “gift of love” and not a “product of the laboratory”.
- The various techniques of artificial human reproduction, “apart from the fact that they are morally unacceptable, since they separate procreation from the fully human context of the conjugal act, have a high rate of failure: not just failure in relation to fertilization but with regard to the subsequent development of the embryo, which is exposed to the risk of death, generally within a very short space of time. Furthermore, the number of embryos produced is often greater than that needed for implantation in the woman's womb, and these so-called "spare embryos" are then destroyed or used for research which, under the pretext of scientific or medical progress, in fact reduces human life to the level of simple "biological material" to be freely disposed of”.
- IVF embryos have two genetic parents, male and female, though artificial gametes would raise the possibility of two genetic mothers. Cloned human embryos have as their genetic parent the donor of the somatic cell nucleus. ‘Cybrids’ have as one ‘parent’ the donor of the somatic cell nucleus. The ‘cybrids’ quasi-mother is not, a woman who donates a “gutted” ovum as for a human clone, but is rather a non-human animal, typically a cow or rabbit.
- Assisted reproduction obscures the concept of parenthood which would be further altered in the draft Bill. For example, subsection 2 (b) of the Bill removes the reference to a child’s need for a father from the licence condition to be imposed under section 13 (5) of the 1990 Act. Clause 60 and Schedule 6 take account of the possibility that a child may have two female parents. The definition of ‘mother’ is relatively straightforward (section 39) as she is the one carrying the child, even if she is not the genetic mother, as in the case of surrogacy. However, a child may have two mothers in the case of a female civil partnership (Clause 48).
- The definition of ‘father’ is much more complicated (clauses 42 and 43). He will usually be accepted as the father of the child if married to the mother in the case of assisted reproduction, unless it can be shown that he did not consent to his wife’s treatment. He is not necessarily the genetic father. Indeed, the genetic father may not be the legally recognized father in cases of artificial insemination (clause 48). Similarly, a woman is not regarded as a mother simply because of egg donation (Clause 53). The woman may withdraw her consent to a man being the father prior to the transfer of gametes or embryos, but he would not be able to stop her going ahead with the pregnancy. If the man informs the woman that he has withdrawn his consent to pregnancy, the woman may still go ahead, if she so wishes.
- Successful cloning after the transfer of a somatic cell nucleus into an enucleated oocyte requires the inserted nucleus to be reprogrammed by the egg cytoplasm to recommence embryogenesis. There are factors within the oocyte cytoplasm which are capable of altering the epigenetic structure of the genome to reset it so as to express the genes necessary for embryonic development rather than those of a mature somatic cell e.g. a skin cell. Cloned animals suffer from a variety of malformations attributable to inappropriate expression of some of their genes and in particular to incomplete reprogramming of embryogenesis.
- There is considerable scientific doubt as to the viability of ‘cybrids’ in which a somatic cell nucleus is transferred into the enucleated egg of another species. To date, most attempts to clone mammals using eggs from distantly related species appear to have only permitted limited embryonic development as far as the blastocyst stage       . Furthermore, even development to the blastocyst stage, in order to derive embryonic stem cells, is not necessarily equivalent to full reprogramming, even when using nuclei and eggs from the same species.
- Further doubt on the survival rates of mixed-species cloned embryos arises from consideration of host mitochondria function, particularly when the species are not closely related      . It would appear that there is a lower developmental potential in oocytes with low numbers of mitochondria. This indicates the importance of functioning mitochondria in embryogenesis    . The preferential replication of donor and recipient mitochondria may also be important in embryonic development        . The studies of Barrientos et al (1998) and Kenyon and Moraes (1997) have shown that there is considerable interaction between nuclear DNA and mitochondria DNA in relation to the formation and function of mitochondria. The interdependence of a large number of gene products coded by both the mitochondrial and nuclear genomes has led to the close evolution of the two genomes in a species-specific manner. However, mitochondria taken from species very similar to Man such as New World and Old World Monkeys, orangutans and lemurs, could not functionally replace human mitochondria in cells. Mitochondria from gorilla, chimpanzee and pigmy chimp were partially successful in restoring oxidative phosphorylation, though oxygen consumption remained 20-34% lower than that of the human parental cell line (Kenyon and Moraes 1997). In addition, it was found that there was a considerable deficiency in the function of mitochondrial complex I in these cells (Barrientos et al, 1998).
- Nuclear transfer can also result in mixed populations of mitochondrial DNA being present in embryos. Furthermore, genes coding for proteins in the electron transfer chain are encoded by the nucleus. It remains to be seen whether the mixing of nuclear genes from one species with mitochondrial DNA genes from another will reduce mitochondrial function. As the human nuclear genome becomes active, it would produce proteins which would migrate to the animal mitochondria, producing mitochondria from both species. This is likely to impair mitochondrial energy production for the cell and may explain the poor viability of such ‘cybrids’.
- Whilst mitochondrial function and energy production may have a significant effect on embryogenesis, there are also known differences in the reprogramming of gene expression in the early stages of embryonic development in different mammalian genera  . There are also similarities between the defects in cloned animals and interspecies hybrids which again suggests that the use of eggs from more distantly related species would lead to even more defects in reprogrammed gene expression      .
- The ultimate test of whether an interspecies hybrid or a ‘cybrid’ embryo would develop into a fully independent living organism would be successful implantation and subsequent gestation. This is currently outlawed. Any embryonic stem cells, or their derivatives, that might be used clinically in humans would first have to be tested in vivo for abnormalities and any propensity to form tumours or develop abnormalities. The draft Bill deals only with research using human embryos in vitro. There are no legislative provisions in the Bill relating to the use of embryonic stem cells in clinical trials in humans. Any expectations that embryo research will provide immediate clinical benefit to patients are therefore misplaced. Indeed, some have argued that such direct clinical developments are unlikely on theoretical and practical grounds.
- Several organizations have argued for the necessity of embryo research in order to provide embryonic stem cell lines for therapeutic purposes. It is argued that embryonic stem cells will play an essential role in regenerative medicine. However, to date there have been no clinical successes with embryonic cell lines, unlike with adult stem cells.
- At the end of this submission (page 11) is a list of 167 references, including reviews and clinical papers in peer review journals regarding the clinical applications of adult stem cells. The list of references is not exhaustive but does illustrate the wider range of circumstances in which adult stem cells have been successful in clinical practice. There is clearly enormous potential for future developments in regenerative medicine and for organ and tissue repair using adult stem cells.
- Autologous bone marrow stem cells have been used for transplantation for a wide range of haematological conditions (refs l00-119) and Immunodeficiency states (refs 95-99). In addition, they have been used for clinical rescue following aggressive chemotherapy for non-haematological malignancy (refs 1-9). There are now a range of autoimmune disease that have been treated with adult stem cells (ref 53-94). An important development in the use of adult stem cells is in the repair or replacement of tissues and solid organs (refs 120-138). Stem cells have also been used for tissue repair (refs 139-141). A particularly exciting development is the potential use of stem cells to repair damaged heart muscle following myocardial infarction (refs 142-159) or nerve cell damage after stroke or other forms of neural damage (refs 160-167).
- The essential argument put forward by those in favour of human embryo research into human disease, is not that embryonic stem cell research will lead to cures, but rather that it may do so at some time in the future. It is argued that such research should be allowed to continue in order to gain the necessary technical skill in handling stem cells and to gain further knowledge from basic scientific research.
- Whilst adult stem cells have already been shown to be of benefit to patients, the therapeutic use, if any, of embryonic cells has not been established. One research group has reportedly derived embryonic stem cells following transfer of nuclei from human skin cells into rabbit eggs. However, a report in the journal Nature described how doubt remains within the research community regarding the feasibility of this approach, which has not been replicated.
- There are important theoretical and practical reasons for doubting the value of cloned embryos and ‘cybrids’ as models for the study of human disease. Indeed, ‘results’ from such experiments may be essentially uninterruptible as the embryos produced in vitro are inherently abnormal. Furthermore, it is difficult to understand the value of studying cells from embryos in vitro as a means of understanding various non-congenital and late-onset conditions such as Parkinson’s disease or Alzheimer’s disease. Researchers into Motor Neurone Disease already have at their disposal a mouse model containing SOD1 mutations. There are also animal models in mice for Down’s syndrome (‘Down’s mouse’) and Huntingdon’s Disease in which affected human genetic material has been inserted into mice.
- From a practical and economic perspective, embryonically derived stem cell therapies would suffer not only from epigenetic defects but would need to be tailored to individual patients. This would be prohibitively expensive in manpower and resources. Such tailor made embryonic cell therapy would only be available (if at all) to those who could afford it. Embryonic stem cell therapies are unlikely to prove attractive to Biomedical companies.
- The overwhelming majority of, and possibly all, cloned embryos are abnormal, and have a high degree of altered gene expression which is further complicated by being somewhat random and therefore unpredictable            . As already indicated above, the use of animal-human ‘cybrids’ is further complicated by the poorly understood interactions between the nuclear genome and animal mitochondria. Moreover, there is no convincing evidence that embryonic stem cells (in contrast to adult stem cells) can be reliably differentiated into normal adult cell types, to be used safely and effectively in clinical practice. According to Professor Sir Martin Evans :”It is also pertinent to observe that cell cultures intended for therapeutic applications in tissue therapy will not be embryonic cells themselves but rather their differentiated derivatives. These cells may or may not have arisen from human embryos and their effectiveness will have to be tested in animal models—i.e. in chimaeras”
- Human cloning has been far more difficult than anticipated. Human eggs are more fragile than eggs of other mammalian species and they do not easily survive the procedures that were successfully used to clone animals. Cloned embryos are generally very abnormal. Those that are sufficiently normal to survive to live birth representing between 0.1 and 2%. Indeed, the usual fate of embryonic stem cells when transplanted into adult animals is that they die.
- It is clear that neither the current legislation, nor the proposed Bill, address the question of the use of embryonically derived stem cell tissue for therapeutic purposes. Furthermore, there are theoretical reasons for believing that embryonic stem cells derived from ‘cybrids’ may pose serious threats to human recipients, even if stem cell lines could be produced, despite the difficulties outlined above.
- The value of using ‘cybrids’ at all has been questioned by the European Society for Human Reproduction and Embryology. “It must be pointed out that this is research, not therapy and that if research showed a possible therapeutic application, all stringent measures in order to prevent risk to patients should be applied”.
- “While not offering the prospect of effective treatments in the short term (nor any guarantee of therapies or cures), they should reduce the need for research on live animals as models for certain diseases…….It is important not to create false hopes that this research will produce cures for debilitating diseases”. Indeed, no-one at present is proposing any serious use of embryonic stem cells in clinical practice. Moreover such activity is already implicitly prohibited in the EU Tissue Directive 2006/86/EC.
- Hitherto, the thorough development of new therapeutic protocols in relevant animal models was a sine qua non in clinical medicine. However, the need for animal experimentation was considered unnecessary with the availability of human IVF embryos. Nevertheless, any embryonic stem cell lines derived from embryos would doubtless be tested in animal models prior to their use in humans because of the risks inherent in the use of such stem cell lines.
- Where ‘cybrids’ are used there is a theoretical risk of the spread of infection across species boundaries. This has occurred already with prions in the case of variant CJD and BSE and viruses (AIDS and avian flu). In an experiment in which human hematopoietic stem cells were injected into fetal pigs, the authors warned that the resulting fused cells were capable of transmitting a pig virus to uninfected human cells, jumping the species barrier.
- A further difficulty with using human embryonic stem (hES) cells for treatment purposes is that the tumourogenic capability of these cells is difficult, if not impossible, to control. This gives multipotent adult progenitor cells a therapeutic advantage over embryonic stem cells. It is quite possible that the tumour formation in cell lines and gene mutations in clones could be potentially worse for the recipients than the disease itself.
- Embryonic cell lines derived from embryos derived from IVF embryos would be at risk from immunological rejection if transplanted into patients. Rejection would not be a problem with the use of adult stem cells derived from the patient. However, to engineer specific cell lines to match the patient would be absurdly expensive and would be confined to the rich.
- The declaration of Helsinki states that: "In research on man, the interest of science and society should never take precedence over considerations related to the well-being of the subject" (III.4). Furthermore, the Council of Europe’s Convention on Human Rights and Biomedicine, signed by 31 out of the 45 Council of Europe Member States (but not the UK) states in Article 18 (2) that “the creation of human embryos for research purposes is prohibited.”
- The theory of human rights is based precisely on the principle of non-exploitation. Human beings must never be regarded as means, but rather as ends in themselves. Human life, particularly in its embryonic stage, is no mere “thing” to be treated like property which can be owned, controlled and manipulated. This is precisely what will be allowed under the Bill which would permit embryos to be possessed, selected, screened, manipulated, modified, stored, processed, transported and destroyed under regulations. The approach taken by the Bill is that “embryos have no right to life which is protected by article 2”. This leaves the human embryo with even less legal protection than a laboratory animal.
- “The value of democracy stands or falls with the values which it embodies and promotes. Of course, values such as the dignity of every human person, respect for inviolable and inalienable human rights, and the adoption of the "common good" as the end and criterion regulating political life are certainly fundamental and not to be ignored. The basis of these values cannot be provisional and changeable "majority" opinions, but only the acknowledgment of an objective moral law which, as the "natural law" written in the human heart, is the obligatory point of reference for civil law itself.”
- The democratic ideal requires protection of the dignity of the human person. Yet, “how is it still possible to speak of the dignity of every human person when the killing of the weakest and most innocent is permitted?” The Human Tissue and Embryos Bill violates the fundamental and inalienable right to life of the human embryo. Fundamental human values and principles are denied in favour of ‘consensus’. Statutory regulation becomes a substitute for moral reasoning and permits practices such as destructive embryo research while bypassing ethical scrutiny. “In this way, any reference to common values and to a truth absolutely binding on everyone is lost, and social life ventures on to the shifting sands of complete relativism. At that point, everything is negotiable, everything is open to bargaining: even the first of the fundamental rights, the right to life”. The use of human embryos or fetuses as an object of experimentation constitutes a crime against their dignity as human beings who have a right to the same respect owed to a child once born, just as to every person. Democracy can” never presume to legitimise as a right of individuals-even if they are the majority of the members of society-an offence against other persons caused by the disregard of so fundamental a right as the right to life”.
- In the consultation on the creation of chimaeras and hybrid embryos and embryo research it was found that: "Of 336 responses that specifically addressed the question, 277 were opposed to the creation of human-animal chimera and hybrid embryos. The consultation document did not seek views on embryo research because the Government had made clear its intention not to propose changes to the fundamental aspects of the current law, including the permissibility of embryo research. However, 227 of the respondents opposed to hybrids and chimeras also stated opposition to embryo research, or such opposition may reasonably be inferred”.
- "In no sphere of life can the civil law take the place of conscience or dictate norms concerning things which are outside its competence", which is that of ensuring the common good of people through the recognition and defence of their fundamental rights, and the promotion of public morality. The Catholic Church has condemned “procedures that exploit living human embryos and foetuses -sometimes specifically "produced" for this purpose by in vitro fertilization-either to be used as "biological material" or as providers of organs or tissue for transplants in the treatment of certain diseases. The killing of innocent human creatures, even if carried out to help others, constitutes an absolutely unacceptable act. The use of embryonically derived cells and tissues would therefore create ethical dilemmas for doctors and also for patients who may be asked to accept such treatments. No one can under any circumstances claim for himself the right directly to destroy an innocent human being even for a therapeutic end.
Ethical status of the human embryo
Inviolable right to life
Role of the family in human procreation.
Cloning and creation of ‘Cybrids’ through interspecies Cell Nuclear Transfer.
Therapeutic applications for adult stem cells
Destructive research on human embryos.
Human rights and the law
Peer-reviewed references showing clinical applications of adult stem
cells that have produced therapeutic benefit for human patients.
(This is meant to be a representative, not a complete, listing of references to illustrate the very wide range of clinical applications for adult stem cells taken from the medical literature).
ADULT STEM CELLS--HEMATOPOIETIC REPLACEMENT
1. Dunkel, IJ; “High-dose chemotherapy with autologous stem cell rescue for malignant brain tumors”. Cancer Invest. 18, 492-493; 2000.
2. Abrey, LE et al.; “High dose chemotherapy with autologous stem cell rescue in adults with malignant primary brain tumors”; J. Neurooncol. 44, 147-153; Sept., 1999
3. Finlay, JL; “The role of high-dose chemotherapy and stem cell rescue in the treatment of malignant brain tumors: a reappraisal”; Pediatr. Transplant 3 Suppl. 1, 87-95; 1999
4. Hertzberg H et al.; “Recurrent disseminated retinoblastoma in a 7-year-old girl treated successfully by high-dose chemotherapy and CD34-selected autologous peripheral blood stem cell transplantation”; Bone Marrow Transplant 27(6), 653-655; March 2001
5. Stiff PJ et al.; “High-dose chemotherapy and autologous stem-cell transplantation for ovarian cancer: An autologous blood and marrow transplant registry report”; Ann. Intern. Med. 133, 504-515; Oct. 3, 2000
6. Waldmann V et al.; “Transient complete remission of metastasized merkel cell carcinoma by high-dose polychemotherapy and autologous peripheral blood stem cell transplantation”; Br. J. Dermatol. 143, 837-839; Oct 2000
7. Tabata M et al.; “Peripheral blood stem cell transplantation in patients over 65 years old with malignant lymphoma--possibility of early completion of chemotherapy and improvement of performance status”; Intern Med 40, 471-474; June 2001
8. Dunkel IJ et al.;”Succesful treatment of metastatic retinoblastoma”. Cancer 89, 2117-2121 Nov15 2000.
9. Koizumi M et al.; “Successful treatment of intravascular malignant lymphomatosis with high-dose chemotherapy and autologous peripheral blood stem cell transplantation”; Bone Marrow Transplant 27, 1101-1103; May 2001
10. Buadi FK et al., Autologous hematopoietic stem cell transplantation for older patients with relapsed non-Hodgkin's lymphoma, Bone Marrow Transplant 37, 1017-1022, June 2006
11. Tabata M et al.; “Peripheral blood stem cell transplantation in patients over 65 years old with malignant lymphoma--possibility of early completion of chemotherapy and improvement of performance status”; Intern Med 40, 471-474; June 2001
12. Kirita T et al.; “Primary non-Hodgkin’s lymphoma of the mandible treated with radiotherapy, chemotherapy, and autologous peripheral blood stem cell transplantation”; Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 90, 450-455; Oct. 2000
13. Peggs KS et al., “Clinical evidence of a graft-versus-Hodgkin’s-lymphoma effect after reduced-intensity allogeneic transplantion”, Lancet 365, 1934-1941, 4 June 2005
14. Laughlin MJ et al.; “Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors”, New England Journal of Medicine 344, 1815-1822; June 14, 2001
15. Ohnuma K et al.; “Cord blood transplantation from HLA-mismatched unrelated donors as a treatment for children with haematological malignancies”; Br J Haematol 112(4), 981-987; March 2001
16. Marco F et al.; “High Survival Rate in Infant Acute Leukemia Treated With Early High-Dose Chemotherapy and Stem-Cell Support”; J Clin Oncol 18, 3256-3261; Sept. 15 2000
17. Laughlin MJ et al.; “Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors”, New England Journal of Medicine 344, 1815-1822; June 14, 2001
18. Ohnuma K et al.; “Cord blood transplantation from HLA-mismatched unrelated donors as a treatment for children with haematological malignancies”; Br J Haematol 112(4), 981-987; March 2001
19. Gorin NC et al.; “Feasibility and recent improvement of autologous stem cell transplantation for acute myelocytic leukaemia in patients over 60 years of age: importance of the source of stem cells”; Br. J. Haematol. 110, 887-893; Sept 2000
20. Bruserud O et al.; “New strategies in the treatment of acute myelogenous leukemia: mobilization and transplantation of autologous peripheral blood stem cells in adult patients”; Stem Cells 18, 343-351; 2000
21. Laughlin MJ et al.; “Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors”, New England Journal of Medicine 344, 1815-1822; June 14, 2001
22. Ohnuma K et al.; “Cord blood transplantation from HLA-mismatched unrelated donors as a treatment for children with haematological malignancies”; Br J Haematol 112(4), 981-987; March 2001
23. Ohnuma K et al.; “Cord blood transplantation from HLA-mismatched unrelated donors as a treatment for children with haematological malignancies”; Br J Haematol 112(4), 981-987; March 2001
24. Elliott MA et al., Allogeneic stem cell transplantation and donor lymphocyte infusions for chronic myelomonocytic leukemia, Bone Marrow Transplantation 37, 1003-1008, 2006
25. Aviles A et al., Biological modifiers as cytoreductive therapy before stem cell transplant in previously untreated patients with multiple myeloma, Annals of Oncology 16, 219-221, 2005
26. Ohnuma K et al.; “Cord blood transplantation from HLA-mismatched unrelated donors as a treatment for children with haematological malignancies”; Br J Haematol 112(4), 981-987; March 2001
27. Bensinger WI et al.; “Transplantation of bone marrow as compared with peripheral-blood cells from HLA identical relatives in patients with hematologic cancers”; New England Journal of Medicine 344, 175-181; Jan 18 2001
28. Damon LE et al.; “High-dose chemotherapy and hematopoietic stem cell rescue for breast cancer: experience in California”; Biol. Blood Marrow Transplant 6, 496-505; 2000
29. Paquette, RL et al., “Ex vivo expanded unselected peripheral blood: progenitor cells reduce posttransplantation neutropenia, thrombocytopenia, and anemia in patients with breast cancer”, Blood 96, 2385-2390; October, 2000.
30. Stiff P et al.; “Autologous transplantation of ex vivo expanded bone marrow cells grown from small aliquots after high-dose chemotherapy for breast cancer”; Blood 95, 2169-2174; March 15, 2000
31. Koc, ON et al.; “Rapid Hematopoietic Recovery After Coinfusion of Autologous-Blood Stem Cells and Culture-Expanded Marrow Mesenchymal Stem Cells in Advanced Breast Cancer Patients Receiving High-Dose Chemotherapy”; J Clin Oncol 18, 307-316; January 2000
32. Kawa, K et al.; “Long-Term Survivors of Advanced Neuroblastoma With MYCN Amplification: A Report of 19 Patients Surviving Disease-Free for More Than 66 Months”; J Clin Oncol 17:3216-3220; October 1999
33. Barkholt L et al., Allogeneic haematopoietic stem cell transplantation for metastatic renal carcinoma in Europe, Annals of Oncology published online 28 April 2006
34. Arya M et al., Allogeneic hematopoietic stem-cell transplantation: the next generation of therapy for metastatic renal cell cancer, Nat Clin Pract Oncol. 1, 32-38, Nov 2004
35. Childs R et al., “Regression of Metastatic Renal-Cell Carcinoma after Nonmyeloablative Allogeneic Peripheral-Blood Stem-Cell Transplantation”, New England Journal of Medicine 343, 750-758; Sept. 14, 2000
36. Childs, RW; “Successful Treatment of Metastatic Renal Cell Carcinoma With a Nonmyeloablative Allogeneic Peripheral-Blood Progenitor-Cell Transplant: Evidence for a Graft-Versus-Tumor Effect:; J Clin Oncol 17, 2044-2049; July 1999
37. Blay JY et al.; “High-dose chemotherapy with autologous hematopoietic stem-cell transplantation for advanced soft tissue sarcoma in adults”; J. Clin. Oncol. 18, 3643-3650; Nov 1 2000
38. Drabko K et al., Megachemotherapy followed by autologous stem cell transplantation in children with Ewing’s sarcoma, Pediatric Transplantation 9, 618-621, 2005
39. Pedrazolli P et al., High dose chemotherapy with autologous hematopoietic stem cell support for solid tumors other than breast cancer in adults, Annals of Oncology published online 17 March 2006
40. Nieboer P et al.; “Long-term haematological recovery following high-dose chemotherapy with autologous bone marrow transplantation or peripheral stem cell transplantation in patients with solid tumours”; Bone Marrow Transplant 27, 959-966; May 2001
41. Lafay-Cousin L et al.; “High-dose thiotepa and
hematopoietic stem cell transplantation in pediatric malignant
mesenchymal tumors: a phase II study”; Bone Marrow Transplant 26,
42. Michon, J and Schleiermacher, G. “Autologous haematopoietic stem cell transplantation for paediatric solid tumors”, Baillieres Best Practice Research in Clinical Haematology 12, 247-259, March-June, 1999.
43. Schilder, RJ et al.; “Phase I trial of multiple cycles of high-dose chemotherapy supported by autologous peripheral-blood stem cells”; J. Clin. Oncol. 17, 2198-2207; July 1999
44. Anagnostopoulos A et al.; “High-dose chemotherapy followed by stem cell transplantation in patients with resistant Waldenstrom's macroglobulinemia”; Bone Marrow Transplant 27, 1027-1029; May 2001
45. Matthes-Martin S et al.; “Successful stem cell transplantation following orthotopic liver transplantation from the same haploidentical family donor in a girl with hemophagocytic lymphohistiocytosis”; Blood 96, 3997-3999; Dec 1, 2000
46. Dispenzieri A et al., Peripheral blood stem cell transplantation in 16 patients with POEMS syndrome, and a review of the literature, Blood 104, 3400-3407, 15 November 2004
47. Cornetta K et al., Umbilical cord blood transplantation in adults: results of the prospective Cord Blood Transplantation (COBLT), Biol Blood Marrow Transplant 11, 149-160, February 2005
48. Cervantes F, Modern management of myelofibrosis, Br J Haematol 128, 583-592, March 2005
49. Kroger N et al., Pilot study of reduced-intensity conditioning followed by allogeneic stem cell transplantation from related and unrelated donors in patients with myelofibrosis, Br J Haematol 128, 690-697, March 2005
50. Thiele J et al., Dynamics of bone marrow changes in patients with chronic idiopathic myelofibrosis following allogeneic stem cell transplantation, Histol Histopathol 20, 87-89, July 2005
51. Rondelli D et al., Allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning in intermediate- or high-risk patients with myelofibrosis with myeloid metaplasia, Blood 105, 4115-4119, 15 May 2005
52. Benesova P et al., [Complete regression of bone marrow fibrosis following allogeneic peripheral blood stem cell transplantation in a patient with idiopathic myelofibrosis] [Article in Czech], Cesk Patol40, 167-171, October 2004
ADULT STEM CELLS—IMMUNE SYSTEM REPLACEMENT
53. Voltarelli JC et al., Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation in Newly Diagnosed Type 1 Diabetes Mellitus, Journal of the American Medical Association 297, 1568-1576, 11 April 2007
54. Burt RK et al., Nonmyeloablative hematopoietic stem cell transplantation for systemic lupus erythematosus, Journal of the American Medical Association 295, 527-535, February 1, 2006
55. Burt RK et al., “Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: getting closer to a cure?”, Blood 99, 768-784, 1 February 2002
56. Wulffraat NM et al.; “Prolonged remission without treatment after autologous stem cell transplantation for refractory childhood systemic lupus erythematosus”; Arthritis Rheum 44(3), 728-731; March 2001
57. Rosen O et al.; “Autologous stem-cell transplantation in refractory autoimmune diseases after in vivo immunoablation and ex vivo depletion of mononuclear cells”; Arthritis res. 2, 327-336; 2000
58. Traynor AE et al.; “Treatment of severe systemic lupus erythematosus with high-dose chemotherapy and haemopoietic stem-cell transplantation: a phase I study”; Lancet 356, 701-707; August 26, 2000
59. Burt, RK and Traynor, AE; “Hematopoietic Stem Cell Transplantation: A New Therapy for Autoimmune Disease”; Stem Cells17, 366-372; 1999
60. Burt RK et al.; “Hematopoietic stem cell transplantation of multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus”; Cancer Treat. Res. 101, 157-184; 1999
61. Traynor A and Burt RK; “Haematopoietic stem cell transplantation for active systemic lupus erythematosus”; Rheumatology 38, 767-772; August 1999
62. Martini A et al.; “Marked and sustained improvement 2 years after autologous stem cell transplant in a girl with system sclerosis”; Rheumatology 38, 773; August 1999
63. Rabusin M et al.; “Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000
64. Rabusin M et al.; “Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000
65. Passweg, JR et al., Haematopoetic stem cell transplantation for refractory autoimmune cytopenia, British Journal of Haematology 125, 749-755, June 2004
66. Rabusin M et al.; “Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000
67. A.M. Feasel et al., "Complete remission of scleromyxedema following autologous stem cell transplantation," Archives of Dermatology 137, 1071-1072; Aug. 2001.
68. Burt RK et al., “Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: getting closer to a cure?”, Blood 99, 768-784, 1 February 2002
69. Burt, RK and Traynor, AE; “Hematopoietic Stem Cell Transplantation: A New Therapy for Autoimmune Disease”; Stem Cells17, 366-372; 1999
70. Kreisel W et al., Complete remission of Crohn’s disease after high-dose cyclophosphamide and autologous stem cell transplantation, Bone Marrow Transplantation 32, 337-340, 2003
71. Burt RK et al., “High-dose immune suppression and autologous hematopoietic stem cell transplantation in refractory Crohn disease”, Blood 101, 2064-2066, March 2003
72. Rabusin M et al.; “Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000
73. Hawkey CJ et al.; “Stem cell transplantation for inflammatory bowel disease: practical and ethical issues”; Gut 46, 869-872; June 2000
74. Rabusin M et al.; “Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000
75. Burt RK et al., “Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: getting closer to a cure?”, Blood 99, 768-784, 1 February 2002
76. Burt RK et al., “Induction of remission of severe and refractory rheumatoid arthritis by allogeneic mixed chimerism”, Arthritis & Rheumatism 50, 2466-2470, August 2004
77. Verburg RJ et al.; “High-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with rheumatoid arthritis: results of an open study to assess feasibility, safety, and efficacy”; Arthritis Rheum 44(4), 754-760; April 2001
78. Rabusin M et al.; “Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000
79. Burt, RK and Traynor, AE; “Hematopoietic Stem Cell Transplantation: A New Therapy for Autoimmune Disease”; Stem Cells17, 366-372; 1999
80. Burt RK et al.; “Hematopoietic stem cell transplantation of multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosis”; Cancer Treat. Res. 101, 157-184; 1999
81. Burt, RK et al., “Autologous hematopoietic stem cell transplantation in refractory rheumatoid arthritis: sustained response in two of four patients”, Arthritis & Rheumatology 42, 2281-2285, November, 1999.
82. I M de Kleer et al., Autologous stem cell transplantation for refractory juvenile idiopathic arthritis: analysis of clinical effects, mortality, and transplant related morbidity, Ann Rheum Dis 63, 1318-1326, 2004
83. Rabusin M et al.; “Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000
84. Burt, RK and Traynor, AE; “Hematopoietic Stem Cell Transplantation: A New Therapy for Autoimmune Disease”; Stem Cells17, 366-372; 1999
85. Saccardi R et al., Autologous HSCT for severe progressive multiple sclerosis in a multicenter trial: impact on disease activity and quality of life, Blood 105, 2601-2607, 15 March 2005
86. Burt RK et al., “Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: getting closer to a cure?”, Blood 99, 768-784, 1 February 2002
87. Mancardi GL et al.; “Autologous hematopoietic stem cell transplantation suppresses Gd-enhanced MRI activity in MS”; Neurology 57, 62-68; July 10, 2001
88. Rabusin M et al.; “Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000
89. Burt, RK and Traynor, AE; “Hematopoietic Stem Cell Transplantation: A New Therapy for Autoimmune Disease”; Stem Cells17, 366-372; 1999
90. Burt RK et al.; “Hematopoietic stem cell transplantation of multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosis”; Cancer Treat. Res. 101, 157-184; 1999
91. Rosen O et al.; “Autologous stem-cell transplantation in refractory autoimmune diseases after in vivo immunoablation and ex vivo depletion of mononuclear cells”; Arthritis res. 2, 327-336; 2000
92. Rabusin M et al.; “Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000
93. Seifert B et al., Complete remission of alopecia universalis after allogenic hematopoietic stem cell transplantion, Blood 105, 426-427, 1 January 2005
94. Kim D-I et al., Angiogenesis facilitated by autologous whole bone marrow stem cell transplantation for Buerger’s disease, Stem Cells 24, 1194-1200, 2006
95. Grunebaum E et al., Bone marrow transplantation for severe combined immune deficiency, Journal of the American Medical Association 295, 508-518, 1 February 2006
96. Cavazzana-Calvo M et al.; “Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease”; Science 288, 669-672; April 28, 2000
97. Banked unrelated umbilical cord blood was used to reconstitute the immune system in 2 brothers with Xlinked lymphoproliferative syndrome and 1 boy with X-linked hyperimmunoglobulin-M syndrome.
98. Ziegner UH et al.; “Unrelated umbilical cord stem cell transplantation for X-linked immunodeficiencies”; J Pediatr 138(4), 570-573; April 2001
99. Amrolia, P. et al., “Non-myelo-ablative stem cell transplantation for congenital immunodeficiencies”, Blood 96, 1239-1246, Aug. 15, 2000.
ANEMIAS AND OTHER HAEMATOLOGICAL CONDITIONS
100. Klein A et al., Hematopoietic stem cell transplantation for severe sickle cell disease, Rev Med Brux. 2005;26 Spec no:Sp23-5
101. Adamkiewicz TV et al., Transplantation of unrelated placental blood cells in children with high-risk sickle cell disease, Bone Marrow Transplant. 34, 405-411, Sept 2004
102. Wu CJ et al., Molecular assessment of erythroid lineage chimerism following non-myelo-ablative allogeneic stem cell transplantation, Exp Hematol. 31, 924-933, Oct 2003
103. Gore L. et al.; “Successful cord blood transplantation for sickle cell anemia from a sibling who is human leukocyte antigen-identical: implications for comprehensive care”, J Pediatr Hematol Oncol 22(5):437-440; Sep-Oct 2000
104. Steen RG et al.; “Improved cerebrovascular patency following therapy in patients with sickle cell disease: initial results in 4 patients who received HLA-identical hematopoietic stem cell allografts”; Ann Neurol 49(2), 222-229; Feb. 2001
105. Wethers DL; “Sickle cell disease in childhood: Part II. Diagnosis and treatment of major complications and recent advances in treatment”; Am. Fam. Physician 62, 1309-1314; Sept. 15, 2000
106. Ayas M et al.; “Congenital sideroblastic anaemia successfully treated using allogeneic stem cell transplantation”; Br J Haematol 113, 938-939; June 2001
107. Gonzalez MI et al.; “Allogeneic peripheral stem cell transplantation in a case of hereditary sideroblastic anaemia”; British Journal of Haematology 109, 658-660; 2000
108. Gurman G et al.; “Allogeneic peripheral blood stem cell transplantation for severe aplastic anemia”; Ther Apher 5(1), 54-57; Feb. 2001
109. Kook H et al.; “Rubella-associated aplastic anemia treated by syngeneic stem cell transplantations”; Am. J. Hematol. 64, 303-305; August 2000
110. Rabusin M et al.; “Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000
111. Yesilipek et al.; “Peripheral stem cell transplantation in a child with amegakaryocytic thrombocytopenia”; Bone Marrow Transplant 26, 571-572; Sept. 2000
112. Tan PH et al., “Unrelated peripheral blood and cord blood hematopoietic stem cell transplants for thalassemia major”, Am J Hematol 75, 209-212, April 2004
113. Sezer O et al.; “Novel approaches to the treatment of primary amyloidosis”; Exper Opin. Investig. Drugs 9, 2343-2350; Oct 2000
114. Ostronoff M et al., “Successful non-myelo-ablative bone marrow transplantation in a corticosteroid-resistant infant with Diamond-Blackfan anemia”, Bone Marrow Transplant. 34, 371-372, August 2004
115. Bitan M et al., Fludarabine-based reduced intensity conditioning for stem cell transplantation of fanconi anemia patients from fully matched related and unrelated donors, Biol Blood Marrow Transplant. 12, 712-718, July 2006
116. Tan PL et al., Successful engraftment without radiation after fludarabine-based regimen in Fanconi anemia patients undergoing genotypically identical donor hematopoietic cell transplantation, Pediatr Blood Cancer, 46, 630-636, May 1, 2006
117. Kohli-Kumar M et al., “Haemopoietic stem/progenitor cell transplant in Fanconi anaemia using HLAmatched sibling umbilical cord blood cells”, British Journal of Haematology 85, 419-422, October 1993
118. Fujii N et al.; “Allogeneic peripheral blood stem cell transplantation for the treatment of chronic active epstein-barr virus infection”; Bone Marrow Transplant 26, 805-808; Oct. 2000
119. Okamura T et al.; “Blood stem-cell transplantation for chronic active Epstein-Barr virus with lymphoproliferation”; Lancet 356, 223-224; July 2000
ADULT STEM CELLS—REPAIR/REPLACEMENT OF SOLID TISSUES
120. Cox-Brinkman J et al., Haematopoietic cell transplantation (HCT) in combination with enzyme replacement therapy (ERT) in patients with Hurler syndrome, Bone Marrow Transplantation 38, 17-21, 2006
121. Staba SL et al., Cord-blood transplants from unrelated donors in patients with Hurler’s syndrome”, NewEngland Journal of Medicine 350, 1960-1969, 6 May 2004
122. Koc ON et al., Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH), Bone Marrow Transplant 215-222; Aug 2002.
123. Horwitz EM et al., “Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone”, Proceedings of the National Academy of Sciences USA 99, 8932-8937; 25 June 2002.
124. Horwitz EM et al., “Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta”, Blood 97, 1227-1231; 1 March 2001.
125. Horwitz, EM et al.; “Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta”; Nat. Med. 5, 309-313; March 1999.
126. Escolar ML et al., “Transplantation of umbilical cord-blood in babies with infantile Krabbe’s disease”, New England Journal of Medicine 352, 2069-2081, 19 May 2005
127. Krivit W et al., “Hematopoietic Stem-Cell Transplantation in Globoid-Cell Leukodystrophy”, New England Journal of Medicine 338, 1119-1127, Apr 16, 1998
128. Tsuji Y et al., Successful nonmyeloablative cord blood transplantation for an infant with malignant infantile osteopetrosis, J Pediatr Hematol Oncol. 27, 495-498, Sept 2005
129. Driessen GJ et al., Long-term outcome of haematopoietic stem cell transplantation in autosomal recessive osteopetrosis: an EBMT report, Bone Marrow Transplantation 32, 657-663, October 2003 Schulz et al., HLA-haploidentical blood progenitor cell transplantation in osteopetrosis, Blood 99, 3458-3460, 1 May 2002
130. Peters C et al., Cerebral X-linked adrenoleukodystrophy: the international hematopoietic cell transplantation experience from 1982 to 1999, Blood 104, 881-888, 1 August 2004
131. Inatomi T et al., Midterm results on ocular surface reconstruction using cultivated autologous oral mucosal epithelial transplantation, American Journal of Ophthalmology 141, 267-275, February 2006; Nishida K et al., Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium, New England Journal of Medicine 351, 1187-1196, 16 September 2004
132. Anderson DF et al.; “Amniotic Membrane Transplantation After the Primary Surgical Management of Band Keratopathy”; Cornea 20(4), 354-361; May 2001
133. Anderson DF et al.; “Amniotic membrane transplantation for partial limbal stem cell deficiency”; Br J Ophthalmol 85(5), 567-575; May 2001
134. Henderson TR et al.; “The long term outcome of limbal allografts: the search for surviving cells”; Br J Ophthalmol 85(5), 604-609; May 2001
135. Daya SM, Ilari FA; “Living related conjuctival limbal allograft for the treatment of stem cell deficiency”; Opthalmology 180, 126-133; January 2001
136. Schwab IR et al.; “Successful transplantation of bioengineered tissue replacements in patients with ocular surface disease”; Cornea 19, 421-426; July 2000.
137. Tsai et al.; “Reconstruction of damaged corneas by transplantation of autologous limbal epithelial cells.”; New England Journal of Medicine 343, 86-93, 2000.
138. Tsubota K et al.; “Treatment of severe ocular-surface disorders with corneal epithelial stem-cell transplantation”; New England Journal of Medicine 340, 1697-1703; June 3, 1999
WOUNDS AND INJURIES
139. Tateishi-Yuyama E et al.; “Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial”; Lancet 360, 427-435; 10 August 2002.
140. Badiavas EV and Falanga V, “Treatment of chronic wounds with bone marrow-derived cells”, Archives of Dermatology 139, 510-516, 2003
141. Warnke PH et al., Growth and transplantation of a custom vascularised bone graft in a man, Lancet 364, 766-770, 28 August 2004
141. Lendeckel S et al., Autologous stem cells (adipose) and fibrin glue used to treat widespread traumatic calvarial defects: case report, Journal of Cranio-Maxillofacial Surgery 32, 370-373, 2004
142. Joseph J et al., Safety and effectiveness of granulocyte-colony stimulating factor in mobilizing stem cells and improving cytokine profile in advanced chronic heart failure, American Journal of Cardiology 97, 681-684, 1 March 2006
143. Blocklet D et al., Myocardial homing of nonmobilized peripheral-blood CD34+ cells after intracoronary injection, Stem Cells 24, 333-336, February 2006
144. Janssens S et al., Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial, Lancet 367, 113-121, 14 January 2006
145. Patel AN et al., Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: a prospective randomized study, Journal Thoracic Cardiovascular Surgery 130, 1631-1638, December 2005
146. Ince H et al., Preservation from left ventricular remodeling by front-integrated revascularization and stem cell liberation in evolving acute myocardial infarction by use of granulocyte-colony-stimulating factor (FIRSTLINE-AMI), Circulation 112, 3097-3106, 15 November 2005
147. Ince H et al., Prevention of left ventricular remodeling with granulocyte colony-stimulating after acute myocardial infarction, Circulation 112, I-73-I-80, 30 August 2005
148. Bartunek J et al., Intracoronary injection of CD133-positive enriched bone marrow progenitor cells promotes cardiac recovery after recent myocardial infarction, Circulation 112, I-178-I-183, 30 August 2005
149. Dohmann HFR et al., Transendocardial autologous bone marrow mononuclear cell injection in ischemic heart failure, Circulation 112, 121-126, 26 July 2005
150. Wollert KC et al., “Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial”, Lancet 364, 141-148, 10 July 2004
151. Britten MB et al., “Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction”; Circulation 108, 2212-2218; Nov 2003
152. Perin EC et al.; “Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure”; Circulation 107, r75-r83; published online May 2003
153. Stamm C et al.; “Autologous bone-marrow stem-cell transplantation for myocardial regeneration”; The Lancet 361, 45-46; 4 January 2003
154. Tse H-F et al.; “Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation”; The Lancet 361, 47-49; 4 January 2003
155. Strauer BE et al.; “Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans”; Circulation 106, 1913-1918; 8 October 2002
156. Strauer BE et al.; “Myocardial regeneration after intracoronary transplantation of human autologous stem cells following acute myocardial infarction”; Dtsch Med Wochenschr 126, 932-938; Aug 24, 2001
157. Menasché P et al. “Myoblast transplantation for heart failure.” Lancet 357, 279-280; Jan 27, 2001
158. Menasché P et al. [“Autologous skeletal myoblast transplantation for cardiac insufficiency. First clinical case.”] [article in French] Arch Mal Coeur Vaiss 94(3), 180-182; March 2001
CHRONIC CORONARY ARTERY DISEASE
159. Strauer BE et al., Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease, Journal of the American College of Cardiology 46, 1651-1658, 1 November 2005
NEURAL DEGENERATIVE DISEASES & INJURIES
160. Shyu W-C et al., Granulocyte colony-stimulating factor for acute ischemic stroke: a randomized controlled trial, Canadian Medical Association Journal 174, 927-933, 28 March 2006
161. Stilley CS et al., Changes in cognitive function after neuronal cell transplantation for basal ganglia stroke, Neurology 63, 1320-1322, October 2004
162. Meltzer CC et al.; “Serial [18F]Fluorodeoxyglucose Positron Emission Tomography after Human Neuronal Implantation for Stroke”; Neurosurgery 49, 586-592; 2001.
163. Kondziolka D et al.; “Transplantation of cultured human neuronal cells for patients with stroke”; Neurology 55, 565-569; August 2000
164. Love S et al., Glial cell line-derived neurotrophic factor induces neuronal sprouting in human brain, Nature Medicine 11, 703-704, July 2005
165. Slevin JT et al., Improvement of bilateral motor functions in patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor, Journal of Neurosurgery 102, 216-222, February 2005
166. Gill SS et al.; “Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease”; Nature Medicine 9, 589-595; May 2003 (published online 31 March 2003)
SPINAL CORD INJURY
167. Lima C et al., Olfactory mucosa autografts in human spinal cord injury: A pilot clinical study, Journal of Spinal Cord Medicine 29, 191-203, July 2006
168. Gordon MY et al., Characterisation and clinical application of human CD34+ stem/progenitor cell populations mobilised into the blood by G-CSF, Stem Cells 24, 1822-1830, July 2006; published online March 30, 2006
169. Terai S et al., Improved liver function in liver cirrhosis patients after autologous bone marrow cell fusion therapy, Stem Cells published online 15 June 2006; DOI: 10.1634/stemcells.2005-0542
170. Atala A et al., Tissue-engineered autologous bladders for patients needing cytoplasty, The Lancet 367, 1241-1246, 15 April 2006
 Evangelium vitae Para 81.
 Should we trust the Scientists? Professor Lord Winston. Gresham Special Lecture, 20 June 2005 http://www.gresham.ac.uk/event.asp?PageId=39&EventId=347
 Congregation for the Doctrine of the Faith, Declaration on Procured Abortion (18 November 1974), Nos. 12-13: AAS 66 (1974), 738.
 Congregation for the Doctrine of the Faith, Instruction on Respect for Human Life in its Origin and on the Dignity of Procreation Donum Vitae (22 February 1987), I, No. 1: AAS 80 (1988), 78-79.
 Apologeticum, IX, 8: CSEL 69, 24.
 For reflection on what would identify an embryo as human, see H Watt, "Embryos and Pseudoembryos: Parthenotes, Reprogrammed Oocytes and Headless Clones", forthcoming in the Journal of Medical Ethics (available online at http://jme.bmj.com/preprint/watt.pdf)
 Clause 14. “In this Act (except in section 4A) – (a) embryo means a live human embryo and does not include and inter-species embryo (ace defined in section 4Q (5)) and (b) references to an embryo include an egg that is in the process of fertilization or is undergoing any other process capable of resulting in an embryo. "
 Conum vitae I, i. Congregation for the Doctrine of the Faith.
 Donum vitae III. Congregation for the Doctrine of the Faith.
 Donum Vitae III. Congregation for the Doctrine of the Faith.
 Evangelium vitae para 81.
 John Paul II, Post-Synodal Apostolic Exhortation, Familiaris Consortio (22 November 1981), 86: AAS 74 (1982), 188.
 Genesis 5:13; Familiaris Consortio. The Role of the Christian Family in the Modern World. John Paul II. 1981`
 Evangelium vitae. Para 11.
 Dominko, T, et al, Bovine oocyte cytoplasm supports development of embryos produced by nuclear transfer of somatic cell nuclei from various mammalian species. Biol Reprod, 1999. 60 (6): p. 1496-1502.
 Lee, B, et al, Blastocyst development after intergeneric nuclear transfer of mountain bongo antelope somatic cells into bovine oocytes. Cloning Stem Cells, 2003. 5 (1): p 25-33.
 Ikumi, S, et al, Interspecies somatic cell nuclear transfer for in vitro production of Antarctic minke whale (Balaenoptera bonaerensis) embryos. Cloning Stem Cells, 2004. 6 (3): . 284-293.
 Lu, F, et al, Development of embryos reconstructed by interspecies nuclear transfer of adult fibroblasts between buffalo (Bubalus bubalis) and cattle (Bos indicus). Theriogenology, 2005. 64 (6): p 1309-1319.
 Murakami, M, et al, Development of interspecies cloned embryos in yak and dog. Cloning Stem Cells, 2005. 7 (2): p 77-81.
 Wen, D C, et al, Hybrid embryos produced by transferring panda or cat somatic nuclei into rabbit MII oocytes can develop to blastocyst in vitro. J Exp Zoolog A Comp Exp Biol, 2005. 303A (8): p 689-697.
 Li, Y, et al, Cloned endangered species taking (Budorcas taxicolor) by inter-species nuclear transfer and comparison of the blastocyst development with yak (Bos grunniens) and bovine. Mol Reprod Dev, 2006. 73 (2): p 189-195.
 Zhao, Z J, et al, Rabbit oocyte cytoplasm supports development of nuclear transfer embryos derived from the somatic cells of the camel and Tibetan antelope. J Reprod Dev, 2006. 52 (3): p 449-459.
 Boiani, M, et al, Variable reprogramming of the pluripotent stem cell marker Oct4 in mouse clones: distinct developmental potentials in different culture environments. Stem Cells, 2005. 23 (8): p 1089-1104.
 Zuckerman, S H, et al, Mitochondrial protein synthesis in interspecific somatic cell hybrids. Somatic Cell Mol. Genet., 1986. 12 (5): p 449-458.
 Kenyon, L and C T Moraes, Expanding the functional human mitochondrial DNA database by the establishment of primate xenomitochondrial cybrids. Proc Natl Acad Sci U.S.A., 1997. 94: p 9131-9135.
 Barrientos, A, L Kenyon, and C T Moraes, Human xenomitochondrial cybrids. Cellular models of mitochondrial complex I deficiency. J Biol Chem, 1998. 273 (23): p 14210-14217.
 Moraes, C T, L Kenyon, and H Hao, Mechanisms of human mitochondrial DNA maintenance: the determining role of primary sequence and length over function. Mol Biol Cell, 1999. 10 (10): p 3345-3356.
 Barrientos, A, et al, Cytochrome c oxidase assembly in primates is sensitive to small evolutionary variations in amino acid sequence. Mol Biol Evol, 2000. 17 (10): p 1508-1519.
 McKenzie, M and I Trounce, Expression of Rattus norvegicus mtDNA in Mus musculus cells results in multiple respiratory chain defects. J Biol Chem, 2000. 275 (40): p 31514-31519.
 McKenzie, M, et al, Functional respiratory chain analyses in murid xenomitochondrial cybrids expose coevolutionary constraints of cytochrome b and nuclear subunits of complex III. Mol Biol Evol, 2003. 20 (7): p 1117-1124.
 El Shourbagy, S H, et al, Mitochondria directly influence fertilisation outcome in the pig. Reproduction, 2006. 131 (2): p 233-245.
 May-Panloup, P, et al, Low oocyte mitochondrial DNA content in ovarian insufficiency. Hum Reprod, 2005. 20 (3): p 593-597.
 Reynier, P, et al, Mitochondrial DNA content affects the fertilizability of human oocytes. Mol Hum Reprod, 2001. 7 (5): p 425-429.
 Santos, T A, S El Shourbagy, and J C St John, Mitochondrial content reflects oocyte variability and fertilization outcome. Fertil Steril, 2006. 85 (3): p 584-591.
 Li, Y, et al, Cloned endangered species taking (Budorcas taxicolor) by inter-species nuclear transfer and comparison of the blastocyst development with yak (Bos grunniens) and bovine. Mol Reprod Dev, 2006. 73 (2): p 189-195.
 Moraes, C T, L Kenyon, and H Hao, Mechanisms of human mitochondrial DNA maintenance: the determining role of primary sequence and length over function. Mol Biol Cell, 1999. 10 (10): p 3345-3356
 Chen, D Y, et al, Interspecies implantation and mitochondria fate of panda-rabbit cloned embryos. Biol Reprod, 2002. 67 (2): p 637-642.
 Steinborn, R, et al, Coexistence of Bos taurus and B indicus mitochondrial DNAs in nuclear transfer-derived somatic cattle clones. Genetics, 2002. 162 (2): p 823-829.
 Chang, K H, et al, Blastocyst formation, karyotype, and mitochondrial DNA of interspecies embryos derived from nuclear transfer of human cord fibroblasts into enucleated bovine oocytes. Fertil Steril, 2003. 80 (6): p 1380-1387.
 Hiendleder, S, et al, Heteroplasmy in bovine fetuses produced by intra- and inter-subspecific somatic cell nuclear transfer: neutral segregation of nuclear donor mitochondrial DNA in various tissues and evidence for recipient cow mitochondria in fetal blood. Biol Reprod, 2003. 68 (1): p 159-166.
 Liu, S Z, et al, Blastocysts produced by nuclear transfer between chicken blastodermal cells and rabbit oocytes. Mol Reprod Dev, 2004. 69 (3): p 296-302.
 Yang, C X, et al, Quantitative analysis of mitochondrial DNAs in macaque embryos reprogrammed by rabbit oocytes. Reproduction, 2004. 127 (2): p 201-205.
 See rewview by St. John et al Reproduction 2004; 127: 631-641
 Beaujean, N, et al, The effect of interspecific oocytes on demethylation of sperm DNA. Proc Natl Acad Sci U.S.A., 2004. 101 (20): p 7636-7640.
 Chen, T, et al, Interspecies nuclear transfer reveals that demethylation of specific repetitive sequences is determined by recipient ooplasm but not by donor intrinsic property in cloned embryos. Mol Reprod Dev, 2006. 73 (3): p 313-317.
 Vrana, P B, et al, Genomic imprinting is disrupted in interspecific Peromyscus hybrids. Nat Genet, 1998. 20: p 362-365.
 Vrana, P B, et al, Genetic and epigenetic incompatibilities underlie hybrid dysgenesis in Peromyscus. Nat. Genet., 2000. 25 (1): p 120-124.
 Hiendleder, S, et al, Nuclear-cytoplasmic interactions affect in utero developmental capacity, phenotype, and cellular metabolism of bovine nuclear transfer fetuses. Biol Reprod, 2004. 70 (4): p 1196-1205.
 Singh, U, et al, Different molecular mechanisms underlie placental overgrowth phenotypes caused by interspecies hybridization, cloning, and Esx1 mutation. Dev. Dynamics, 2004. 230 (1): p 149-164.
 Zechner, U, et al, Divergent genetic and epigenetic post-zygotic isolation mechanisms in Mus and Peromyscus. J Evol Biol, 2004. 17 (2): p 453-460.
 Chen, Y, et al, Embryonic stem cells generated by nuclear transfer of human somatic nuclei into rabbit oocytes. Cell Res, 2003. 13 (4): p 251-263.
 Dennis, C, Cloning: Mining the secrets of the egg. Nature, 2006. 439 (7077): p 652-655.
 Reik, W et al (2001). Sci 293: 1089-1093. "Epigenetic Reprogramming in Mammalian Development."
 Dean, W et al (2001). Proc. Natl. Acad. Sci. USA 98: 13734-13738. "Conservation of Methylation Reprogramming: Aberrant Reprogramming in Cloned Embryos."
 Han, Y M et al, (2003). Theriogenoloy 59: 33-44. "Nuclear Reprogramming of Cloned Embryos Produced in vitro."
 Ohgane, J et al (2001). Genesis 30: 45-50. "DNA Methylation Variation in Cloned Mice."
 Humpherys, D et al (2001). Sci. 293: 95-97. "Epigenetic Instability in ES Cells and Cloned Mice.
 Bourc'his, D et al (2001). Curr. Biol. 11: 1542-1546. "Delayed and Incomplete Reprogramming Patterns in Bovine Cloned Embryos."
 Rideout III, W M et al 2001. Sci 293: 1093-1098. "Nuclear Cloning and Epigenetic Reprogramming of the Genome."
 Fairburn, H R et al (2002). Curr. Biol. 12: R68-R70. "Epigenetic reprogramming: how now, cloned cow?”
 Slimane-Bureau, W C and King, W A (2002). Cloning and Stem Cells 4: 319-329. "Chromosomal Abnormalities: A Potential Quality Issue for Cloned Cattle Embryos."
 Boiani, M et al (2002). Genes and Dev. 16: 1209-1219. "Oct4 Distribution and Level in Mouse Clones: Consequences for Pluripotency."
 Kang, Y K et al (2001). Nat Genet. 28: 173-177. "Aberrant methylation of donor genome in cloned bovine embryos."
 Kang, Y K et al (2002). EMBO J. 21: 1092-1100. "Limited Demethylation Leaves Mosaic-Type Methylation States in Cloned Bovine Pre-Implantation Embryos."
 Memorandum 29. Jan 2007
 Submission from the European Society for Human Reproduction and Embryology. Memorandum 8. Jan 2007.
 Submission from the Institute of Biology Memorandum 12. Jan 2007.
 Commission Directive 2006/86/EC of 24 October 2006 implementing Directive 2004/23/EC of the European Parliament and of the Council as regards traceability requirements, notification of serious adverse reactions and events and certain technical requirements for the coding, processing, preservation, storage and distribution of human tissues and cells.
 Chimeras in the crosshairs, Nature Biotechnology, Vol 24 No. 5 May 2006.
 ] Cell replacement therapy-are MAPCs the answer? Published online 16 Jan 2007, doi:10.1084/jem.2041iti1, The Journal of Experimental Medicine. Many other examples can be found at www.cloning.org.uk.
 Convention on Human Rights and Biomedicine. http://conventions.coe.int/Treaty/en/Treaties/Word/164.doc
 Human Tissue and Embryos (draft) Bill. May 2007. p 122.
 Evangelium vitae. Para 70.
 John Paul II, Address to the Participants at the Study Conference on “The Right to Life and Europe”, 18 December 1987: Insegnamenti, X, 3 (1987), 1446-1447.
 Evangelium Para 20.
 Charter of the Rights of the Family (22 October 1983), article 4b: Vatican Polyglot Press, 1983.
 Evangelium vitae. Para 71.
 Supplementary evidence from the Department of Health following the evidence session on 28 February 2007 to the Science and Technology Committee.
 Congregation for the Doctrine of the Faith, Instruction on Respect for Human Life in its Origin and on the Dignity of Procreation Donum Vitae (22 February 1987), III: AAS 80 (1998), 98
 Second Vatican Eucumenical Council, Declaration on Religious Freedom Dignitatis Humanae, 7.
 Evangelium vitae. Para 63.
 Congregation for the3 Doctrine of the Faith. Donum vitae. Introduction para 5. See also Catechism of the Catholic Church para 2258.
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