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Stem Cell Research: Immortality Or a Healthy Old Age?

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Stem Cell Research: Immortality Or a Healthy Old Age? European Journal of Endocrinology (2004) 151 U7–U12 ISSN 0804-4643 Stem cell research: immortality or a healthy old age? Christine Mummery Hubrecht Laboratory, Netherlands Institute for Developmental Biology and the Interuniversity Cardiology Institute of the Netherlands, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands (Correspondence should be addressed to C Mummery; Email: [email protected]) Abstract Stem cell research holds the promise of treatments for many disorders resulting from disease or trauma where one or at most a few cell types have been lost or do not function. In combination with tissue engineering, stem cells may represent the greatest contribution to contemporary medicine of the present century. Progress is however being hampered by the debate on the origin of stem cells, which can be derived from human embryos and some adult tissues. Politics, religious beliefs and the media have determined society’s current perception of their relative value while the ethical antipathy towards embryonic stem cells, which require destruction of a human embryo for their derivation, has in many countries biased research towards adult stem cells. Many scientists believe this bias may be premature and basic research on both cell types is still required. The media has created confusion about the purpose of stem cell research: treating chronic ailments or striving for immortality. Here, the scientific state of the art on adult and embryonic stem cells is reviewed as a basis for a debate on whether research on embryonic stem cells is ethically acceptable. European Journal of Endocrinology 151 U7–U12 Introduction was referred to as ‘transdifferentiation’ or adult stem cell ‘plasticity’. Stem cells are primitive cells with the capacity to self- In 1998, the first stem cell lines were derived from renew (divide and produce more of themselves) or to human blastocyst stage embryos (Fig. 1) by Thomson differentiate to specialized cells such as bone, brain et al. (1). This milestone in cell biological research and heart cells. Stem cells are often placed in one of had been preceded by more than 30 years of research two categories: adult stem cells derived from adult or on another very similar cell type, an embryonal carci- fetal tissues and embryonic stem (ES) cells derived noma or teratocarcinoma stem cell, derived from a from very early (mouse or human) embryos at the blas- spontaneous testis tumour found in mice and men tocyst stage of development (Fig. 1) prior to implan- (Fig. 1). In mice, teratocarcinomas can be formed tation in the uterine wall. experimentally by transferring young embryos to extra- Stem cells of bone marrow have been used for dec- uterine sites, for example, under the skin or kidney cap- ades in the successful treatment of blood disorders sule. Stem cells were derived directly from early mouse such as leukemia. Bone marrow transplantation to a embryos as mouse ES cells in 1981, circumventing the patient whose own bone marrow has been destroyed necessity of generating a tumour as an intermediate as part of treatment will allow the patient to start (2, 3). The way was then already open to deriving regenerating blood cell lineages and forming blood human ES cell lines as assisted reproduction by in with a normal cellular composition. Likewise, a skin vitro fertilization was becoming clinically routine. wound will result in stem cells in the basal layers Embryos were being discarded even after three to four resuming proliferation and differentiating to all cell had been simultaneously transferred to a patient types present in normal skin in a manner that recon- because no methods had been developed for successful structs the dermal and epidermal layers. Convention- freezing. These first attempts were not successful and ally, adult or tissue-specific stem cells in adults were took place under circumstances where there was no regarded as having the ability to proliferate at times of legislation governing human embryo research. tissue damage and to differentiate to the cell types in In the mid 1980s it became possible to freeze the tissue in which they were found. Exceptionally, in embryos and therefore sources dried up; legislation sex non-matched organ and bone marrow transplants, was developed in several countries that would even- where, for example, tissue from a male donor was given tually govern human embryo research. Thomson’s to a female recipient, there were occasional reports of article clearly demonstrated that the human ES cell some cells being found in multiple organs. They had lines that he had derived were immortal and pluripo- apparently adopted the phenotype of the local tissue. tent, i.e. they could form derivatives of the three pri- These observations provided the first evidence of what mary germ layers and in principle all tissues of the q 2004 Society of the European Journal of Endocrinology Online version via http://www.eje.org Downloaded from Bioscientifica.com at 09/26/2021 09:09:37AM via free access U8 C Mummery EUROPEAN JOURNAL OF ENDOCRINOLOGY (2004) 151 Figure 1 Pluripotent human stem cells are found in teratocarcinomas and in the inner cell mass (ICM) of blastocyst stage embryos. human body. The implications for cell-based therapies ethics believe that life begins at fertilization, other were immediately obvious and a list of diseases or ail- beliefs consider 40 days after conception as the crucial ments for which human ES cells might be useful time point in determining the moral status of the because only one or, at most, a few cell types were embryo. affected was easy to draw up (Table 1). The ‘price’ of In the following sections, the current status of this research, however, is destruction of human research on adult and ES cells (Table 2) is reviewed embryos that have the potential to become new (4). The conclusion is that research on neither adult human beings. The fact that these embryos were des- nor ES cells is sufficiently advanced for a definitive and tined to be discarded and, by implication, destroyed exclusive choice on whether one is better or worse because the gamete donors who had lead to their for- than the other as a basis for developing a broad range mation no longer wished to continue with their of stem cell therapies. Each is most likely to have its parent programme, was for many not an argument to own niche in therapy. In some cases the best option redirect their fate towards stem cell derivation however may be combined adult and ES cell therapy. If it were noble the cause of curing chronic disability. The simul- already proven that human ES cells are useful in taneous revisiting by a number of scientists of the abil- curing patients it would be much easier to justify sacri- ity of adult stem cells to transdifferentiate may have, in ficing embryos for those cures. However, it is not proven part, derived from the aversion to embryo destruction. and it is under those circumstances that we have to It is of note, however, that not all societies or religions decide whether derivation of new human ES cell lines adopt the same point of view: while Christian-based is justified for the purposes of research in the light of Table 1 Examples of ailments for which solutions in stem cell therapy are being sought. Table 2 Stem cell origins. Stroke Stem cells are found in: Parkinson’s disease 1. Adult tissues: all tissues and organs that can repair themselves Diabetes after damage or regenerate have adult stem cells. Examples Heart failure are: skin, bone marrow/cord blood, intestine, brain, liver, fat. Vascular disease Not ethically sensitive but there are very few cells present in Arthritis normal tissue and only a few different cell types can be formed. Multiple sclerosis 2. Embryos: embryonic stem cells. Spinal cord lesions Ethically very sensitive as destruction of the embryo is necessary but many cells available in the laboratory and all In general diseases associated with increasing age (in italics) where one or cells of the human body can be formed. at most a few cells types have been destroyed or malfunction. www.eje.org Downloaded from Bioscientifica.com at 09/26/2021 09:09:37AM via free access EUROPEAN JOURNAL OF ENDOCRINOLOGY (2004) 151 Stem cell research U9 the current availability of a number of human ES cell derived from his own bone marrow and implanted; lines already established. bone fide bone then developed and functioned as a normal ribcage. A second example concerned a young woman who underwent surgery for removal of a Adult stem cells in clinical practice or large tumour in her jaw. This left her with a serious clinical trials facial disfigurement. Again, tissue engineers recon- There are already a number of clinical applications for structed a bone matrix but now in the form of a jaw. several types of adult stem cells derived from different Her stem cells were seeded to the matrix and bone tissue sources (see Table 3). Some of these are autolo- developed in situ of such quality that artificial teeth gous, a patient receiving some of his own stem cells could be implanted and the jaw functioned essentially to repair a particular organ, others are heterologous as normal. This is an area being very actively pursued. and the stem cells are provided by a donor. The main drawback is an age limitation of the suit- ability and numbers of stem cells. Above the age of Pancreas duct stem cells These stem cells are cur- 50 years, the method generally does not work. Another rently being tested in clinical trials for the treatment drawback is the size of the engineered implant; the of ‘brittle’ diabetes. This form of diabetes is very seeded cells require adequate nutrients and blood severe, difficult to control with insulin and patients supply, and therefore only tend to survive well in the are often not aware of an imminent hyperglycemic inci- outermost regions of the bone matrix.
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