SIMPLE FACTS ABOUT STEM CELLS
M.-L. Labat1, G. Milhaud2, J.-M. Le Méné3
1.CNRS Ecole Nationale Vétérinaire d’Alfort, 94704 Maisons-Alfort, France
2. Académie de Médecine, 75005 Paris, France
3. Fondation Jérôme Lejeune, 75005 Paris, France
ABSTRACT
When Professor Jerôme Lejeune told us that all necessary information to give birth to a unique human being was present in the fertilized egg, and that therefore the first stem cell, the egg, was fully human, the knowledge of the great geneticist was joining the thinking of the man of faith. Four years after Professor Lejeune died, J. Thomson in 1998, reported that he had derived stem cells from embryos created during in-vitro fertilization treatment but not needed by their parents and claimed that they were going to cure most frightening degenerative disorders, such as diabetes, Parkinson’s and Alzheimer’s diseases. That gave rise to a worldwide political and ethical debate about the use of human embryos as a medicine. Therapeutic cloning was then proposed to avoid supposed inevitable rejection if stem cells coming from any ‘surnumerary’ embryos were transplanted into patients. Then, another worldwide debate started: should human therapeutic cloning be authorized? While these hot debates were going on, scientists discovered that embryonic stem cells did not follow the same transplantation rules as other tissues and that they were not rejected when mismatching the recipient. Logically, the political debate, on therapeutic cloning, now pointless should have immediately stopped. Surprisingly, it is still going on.
While these debates were going on, major discoveries changed our views on stem cells presence in adult organism. During the past few years, stem cells have been found in any organ where they have been looked for, even in brain. They have been called ‘adult’ stem cells, because present in the adult. However, in order to distinguish them from hematopoietic stem cells, the expression ‘organ stem cells’ seems more appropriate. Certain similarities seem to exist between embryonic and adult stem cells: both are able to differentiate into the different kinds of cells needed for tissue repair. But there are major differences. Embryonic stem cells are laboratory devices deviated from their initial aim that is to make a baby while adult stem cells are mastered cells specifically designed for maintenance of the integrity of the organism and tissue repair. Tissue repair, like other immunological reaction has to be initiated, to develop and to know how to terminate. That means that adult stem cells have to be tightly controlled. Many ‘check-points’ probably exist: one of them take place at the blood level where a circulating stem cell is under phagic T lymphocytes control. Failure in this control may lead to fibrosis and/ or malignancy.
Embryonic stem cells are probably too immature to have acquired the ability to be regulated, a necessary characteristic for a safe transplantation which has otherwise an unlimited proliferative potential. These scientific questions should have been studied in animals before claiming embryonic stem cells virtues to cure degenerative diseases. It has simply been assumed that embryonic stem cells transplantation should follow the same rules as specialized cells. This is not the case: when injected into mismatching recipients, embryonic stem cells are not rejected. Hence, transplantation rules for stem cells remain to be defined using animals: the problem of embryonic stem cells seems more a mater of ‘control’ than one of ‘rejection’. This knowledge is a necessary preliminary to insure a safe therapeutic use. Hence, in the present state of knowledge, the worldwide ethical and political debate concerning embryonic stem cells is just nonsense.
All efforts should be made to better understand adult stem cells. We need to better understand why their regulation fails in fibrosis and cancer. We need to learn how their proliferation can be stimulated to treat diseases in which they fail to be recruited and the best ways to transplant them.
Professor Jerôme Lejeune’s testimony is more than ever topical. At a time when direct transfer of technologies from veterinarian art to medicine is liable to change the proper nature of our species, his message is clear: the embryo is human from conception and belongs to no one.
A human being is a mammal with single and internal ovulation that new biotechnologies are transforming into a mammal with external polyovulation. Initially, the aim was to help sterile patients. However, by doing so, the human embryo became accessible to experimentation, with the consequences we see now: preimplantation diagnosis with the risk of eugenism, extraction of stem cells from the human embryo considered as a medical tool and may be to-morrow reproductive cloning.
In November 1998 (1), J.A. Thomson reported that with his company-funded team he had derived stem cells from embryos created during in-vitro fertilization treatment that were not needed any more by their parents. These blastocyst-derived cell lines were capable of unlimited proliferation in vitro, while maintaining the potential to differentiate into derivatives of all three embryonic cell layers. In December 1998, the author testified before the United States Senate (2) that these embryonic stem cells were going to cure all most frightening degenerative disorders, such as diabetes, Parkinson’s and Alzheimer’s diseases. This information was immediately taken over by the media since immortality has always held a powerful grip on popular imagination. The virtues of these embryonic stem cells were extolled by desperate patients and lobbying politicians in order to promote research on them. Since extraction of embryonic stem cells implies the destruction of a human embryo, a worldwide political and ethical debate arose about the use of the human embryo as a medicine in stem cell therapy.
Stem cell therapy aims at replacing lost or worn-out cells by new ones. Clearly, hematopoietic stem cells have now been successfully used for more than three decades to reconstitute the hematopoietic tissues after myeloablation and to treat leukemia. The few past years have seen a rapid development in the field of adult stem cells that have now been found present in all the tissues where they have been looked for, including the brain. Hence the debate about embryonic stem cells is sometimes set out in the media as a debate between those who want to promote human adult stem cell research and those who support embryonic stem cell research.
WHAT ARE HUMAN EMBRYONIC STEM CELLS?
Embryonic stem cells are laboratory devices resulting from the recent availability of human embryo experimentation, this being the consequence of a direct transfer of technologies from the veterinarian art to medicine.
The human being is a mammal with single and internal ovulation that new biotechnologies are transforming into a mammal with external polyovulation. Initially, the aim was to help sterile patients. However, the technique of in vitro fertilization results in the creation of more embryos than needed by the parents to complete their families.
These ‘surnumerary-embryos-with-no-parental-project’, stocked in liquid nitrogen (cryopreservation), are usually the ones used to derive embryonic stem cells, though some have been created deliberately. Embryonic stem cells are extracted from embryos at the blastocyst stage (day five after fertilization). After dissociation of the inner mass of the human blastocyst, the cells are first grown on a feeder layer of irradiated mouse embryonic fibroblasts. After 9 to 15 days of culture, the outgrowths are harvested and replated. Then sometimes, at random, cell lines appear in the culture. They are selected by their prolonged undifferentiated proliferation characteristics while retaining the ability to differentiate into the three embryonic germ-layers. These are the so-called embryonic stem lines.
On 9th August 2001, President Bush (3) announced that federal funds might be awarded for research using human embryonic stem cell lines that met certain criteria:
- embryonic stem cell lines should have been initiated prior to 9:00 p.m. EDT on 9th
August 2001.
- These stem cells must have been derived from an embryo that was created for reproductive purposes and was no longer wanted by the parents.
- In addition, informed consent must have been obtained from the parents for the donation of the embryo and that donation must not have involved financial inducements.
But what does ‘donation’ and ‘informed consent’ mean when a human embryo is at stake?
From an ethical point of view the following questions arise:
- Who does the human embryo belong to if not to itself?
- When do human beings begin? Any geneticist knows that all the necessary information to make a new human being is present in the first cell, the zygote, that results from the fertilization of the egg by the spermatozoid.
These questions cannot be evaded. When at an April 2002 conference, Senator A Specter (Penn, USA) was asked by a reporter, within the context of embryonic stem cell research, when life begins, Senator Specter replied: ‘I haven’t found it helpful to get into the details”(4). This cannot be considered an acceptable answer to a fundamental question dealing with the future of our species.
However, a question remains: what should we do with the leftover embryos that were created for reproduction?
HAS RESEARCH CONCERNING HUMAN EMBRYONIC STEM CELLS BEEN REALLY CARRIED OUT IN A TRUE SCIENTIFIC WAY?
Thomson indicated in his paper (1) and his testimony (2) about human embryonic stem cells that strategies to prevent immune rejection of the transplanted cells needed to be developed. These strategies could include banking ES cell lines with defined major histocompatibility complex backgrounds, or genetically manipulating ES cells to reduce or actively combat immune rejection.
It was taken for granted that transplantation rules for embryonic stem cells should follow the usual rules governing tissue transplantation and be rejected if mismatching the recipient.
Since the isolation of human embryonic stem cells occurred less than two years after the birth of Dolly, the first cloned sheep (5), human therapeutic cloning was proposed as the most convenient strategy to avoid rejection supposed inevitable if using stem cells coming from any “surplus” embryo.
Then, another worldwide debate started: should human therapeutic cloning be authorized?
While these hot debates were going on, scientists discovered that embryonic stem cells did not follow the same transplantation rules as the other tissues and that they were not rejected when mismatching the recipient (6-7).
Logically, the pointless political debate on therapeutic cloning should have immediately stopped. Surprisingly, it is still going on.
At first glance, the absence of rejection of mismatching embryonic stem cells appears to be in favour of their therapeutic use. Scientifically, that is definitely not the case: this absence of rejection means that the transplanted stem cells cannot be controlled by the host. Tissue repair, like all other immune responses, must be initiated, must develop and finally must terminate. Once the repair process is completed, the stem cells have to be deactivated. Studies about the adult stem cells regulation (also called organ stem cells or somatic stem cells) state that stem cells transplantation rules are completely different from those of other cells of the organism (8-9). As we are going to see, transplanted stem cells need to match the tissue type of the host:
- not to avoid rejection, as in usual case
- but to allow destruction, in case of excessive accumulation. This regulation is accomplished by a special subpopulation of T lymphocytes called phagic T lymphocytes.
The necessary molecules for phagic T lymphocytes activation are not found on embryonic stem cells membranes. Therapeutic cloning cannot solve this problem due to the embryonic nature of the cells.
One of the characteristics of embryonic stem cells is their high potential of proliferation. This was presented as a great advantage, providing a potentially unlimited source of different cell types for transplantation therapies (1) (2).It is worth not to forget that in the 1980’s when, for the first time, early workers isolated these stem cells in mice, they indicated that “A cell line directly derived from normal preimplantation mouse embryos forms teratocarcinomas when injected into mice”. (10)
The high potential of embryonic stem cells proliferation associated to the host inability to control such cells might lead to their excessive accumulation and put the patient at risk of developing fibrosis, malignancies or disorders similar to that reported when patients with Parkinson’s disease were transplanted with foetal neurons (11-12).
According to the authors, embryonic stem cells are supposed to be differentiated into the needed type of cells before transplantation. But, first of all, it might be difficult to differentiate 100% of the proliferating cells and therefore to avoid contamination of the transplant with undifferentiated stem cells that have kept their full proliferative potential. Moreover up to now it has not been possible to direct embryonic stem cells differentiation into only one precise cell type (13).
For these reasons, the ethical and political debates seem premature since embryonic stem cells control, a preliminary condition to the feasibility of their transplantation, still have to be carefully studied. These studies should be carried out on animals.
A FEW WORDS ABOUT THERAPEUTIC AND REPRODUCTIVE CLONING
As mentioned above human therapeutic cloning was proposed to solve a false problem.
Therapeutic cloning is often opposed to reproductive cloning. Actually it is the same thing. In both cases, the nucleus of an egg is replaced by a somatic cell nucleus and a human embryo is created in vitro. In therapeutic cloning, the embryo is destroyed at the blastocyst stage in order to derive embryonic stem cells, while in reproductive cloning the embryo is implanted into a woman’s womb.
In fact, a real clone cannot exist. That is very well illustrated by ‘copy-carbon’, the first cloned cat. The cloned cat was expected to have the same fur as the somatic cell nucleus donor, hence the name ‘copy-carbon’ that it was given at birth. But it turned out not to be the case and the clone had a different fur (14). This is due to the fact that the genes coding for the pigments of the fur are controlled by epigenetic factors and are expressed at random in each cell.
The Council of Europe has included the interdiction of human reproductive cloning in the additional protocol of the Oviedo convention on human rights and bioethics that France should ratify after the vote of the bioethical law. But the adoption of an international convention under the aegis of the United Nations has not been brought to a successful conclusion yet. That means that in most countries human cloning is not clearly forbidden. Certain countries like the United States want to forbid both therapeutic and reproductive cloning, although private companies such as Advanced Cell International (Worcester, Mass) openly continue to work on human therapeutic cloning. Other countries, such as Great Britain, want only reproductive cloning to be forbidden, therapeutic cloning being already authorized under certain conditions and Belgium is very likely to adopt this position soon.
However, last December, the Quebec-based raelian movement announced the birth of a cloned baby but no scientific tests came to support that claim.
ADULT ORGAN STEM CELLS ARE MASTERED TOOLS SPECIFICALLY DESIGNED FOR TISSUE REPAIR.
Adult organ stem cells are also called somatic stem cells in order to distinguish them from hematopoietic stem cells known already for decades. Organ adult stem cells are found buried in the organs, in bone marrow and in blood.
It has been known for decades that certain kinds of stem cells lurk in rapidly and permanent self-renewing adult tissues, such as skin and gut epithelium. Permanent although less rapid, bone remodelling takes place throughout life and involves mesenchymal stem cells, that have been isolated for many years in animals (15) and more recently in human being (16).
It is only recently that organ stem cells have been isolated from organs where they proliferate and differentiate essentially in situations of stress and trauma: they are also called ‘reserve stem cells’. They have been found in all the organs where they have been looked for, particularly in striated muscle (17), liver (18), pancreas (19) hair follicle bulge where they provide stem cells for hair and skin epidermis(20) , dermis (21-22), the heart (23), prostate (24), kidney (25), teeth (26-27) . They have also been found in human spinal cord (28) .Even neural stem cells able to self-renew and to give rise to neurons, astrocytes and oligodendrocytes were found in human brain (29-30), disproving the long-standing dogma due to Ramon Y Cajal according to which human brain could not grow new neurons in adult life. Neural stem cells have also been isolated from the foetal human brain (31) and even successfully cultured from the brain of recently deceased children and adults (32).
In 1999, it was reported that stem cells taken from the brain of adult mice could change their destiny and give rise to blood cells when grown in an embryonic environment (33) or could differentiate into muscle cells when implanted into muscle (34). These experiments indicated that the reprogramming of adult stem cells can take place directly from one tissue type to another, depending on the environment: stem cells were said to have ‘plasticity’. It was the end of another dogma according to which, stem cells from a given organ can only give rise to specialized cells of that organ. Doubt has been casted however on the pluripotency of organ stem cells and fusion was proposed as the mechanisms responsible for the observed change of phenotype of cells derived from stem cells (35-40). However, recent studies dealing with adult organ stem cells present in bone marrow re-examined this question and confirmed the plasticity of adult organ stem cells.
Adult organ stem cells present in bone marrow
The pluripotency of adult stem cells i.e. their ability to give rise to all cells present in the adult organism has been best established in bone marrow. Long known as a source of hematopoietic stem cells, bone marrow now appears as a source of pluripotent organ stem cells able to give rise to connective tissue, cartilage, bone, fat cells (15-16), muscle cells(41), including cardiomyocytes (42) and liver cells (43-46), as well as endothelial cells (47-48), lung cells (49), and even neural cells (50-52). Bone marrow derived cells have also been found to participate in cutaneous wound healing (53)
A single adult bone marrow-derived stem cell was found able to differentiate into epithelial cells of the liver, lung, gut, and skin (54). A subpopulation of mesenchymal stem cells (MSCs) was isolated that have the potential for multilineage differentiation and was called multipotent adult progenitor cells (MAPCs) (55). MAPCs can differentiate in vitro into endothelial cells (56), hepatocyte-like cells (57). MAPCs were found to differentiate at the single cell level, into mesenchymal cells, and also cells with visceral mesoderm, neurectoderm and endoderm characteristics, when injected into an early blastocyst.(58-60). Whether or not MAPCs and MSCs represent two distinct sub-populations of bone marrow derived stem cells has been questioned (61)
However, the pluripotency of organ stem cells present into the bone marrow seems to be well established (62-63).The possibility that fusion could account for observed ‘plasticity’ was studied and excluded in experiments showing that bone marrow cells transdifferentiated into kidney mesangial cells (64), neurectoderm and microglia (65) and neurons (66).
Taken together, these findings favour the existence of a pluripotent stem cell in adults, able to give rise to different types of cells depending on the microenvironment.
Different types of stem cells present in blood have been found able to give rise to fibroblasts (67-68), myofibroblasts (69) bone (67) (70) cartilage (71), muscle cells (72), hepatocytes (43-46), and endothelial cells (47). Because independently studied by authors whose interest focused on particular tissue types, these stem cells have been described as different. However, considering the now known pluripotency of adult stem cells mentioned above, we postulated that these adult stem cells present in blood might well represent one single population of pluripotent stem cells in homeostatic equilibrium with the “reserve”stem cells buried in the organs (8). In blood, they have a monocytic phenotype, they stain for non specific esterases and express monocytic markers such as CD14 and CD68, including HLA-DR molecules (8)(67)(69)(71)(73). These findings have been confirmed recently by another team (74). Cultured in vitro, once they have adhered, they spontaneously differentiate into different types of cells among which fibroblasts (called neofibroblasts) (8) (67)(69)(71)(73), reminiscent of embryonic human stem cells in culture (13).
A neural crest origin of these human stem cells has been postulated since 1997 (26). They spontaneously express neural markers such as neurofilament 160, neuron specific enolase, synaptophysin, glial fibrillary protein (75), and nestin (76).
These adult stem cells are normally almost quiescent. Under precise circumstances, such as tissue repair, these stem cells carried by blood may be recruited on the lesion site where they may proliferate and participate in the regeneration of the damaged tissue. Indeed, such an important cell has to be tightly controlled.
Time-lapse microcinematography shows how a subpopulation of CD4+ T lymphocytes, called phagic T lymphocytes, destroy the stem cells once they have adhered to the support and started to differentiate in vitro. These stem cells that express constitutively HLA-DR molecules, are both the activators and the targets of phagic T lymphocytes that adhere to them penetrate and circulate into them until the stem cells ‘explode’ (8) (73). It is a beneficial exception to self-tolerance, restricted to normal stem cells, which avoids their accumulation out of purpose and terminates the healing process.
In disorders such as fibrosis and malignancy (chondrosarcoma), these circulating stem cells proliferate, escape destruction by phagic T lymphocytes and accumulate, giving rise in vitro to a ‘tissue’ evoking the disease of the patient (67)(69)(71).
On the other hand, it is suggested that excessive activity of phagic T lymphocytes may lead to autoimmune diseases (8).
Only normal stem cells can be destroyed by phagic T-lymphocytes in case of accumulation with no repair purpose. Since this destruction process is class II MHC (HLA-DR) restricted, it follows that transplanted foreign cells cannot activate phagic T lymphocytes and therefore cannot be controlled. This may explain the observation that human mesenchymal stem cells are not rejected neither when transplanted in a xenogenic fetal recipient even after the expected development of immunologic competence (78) nor in xenogenic immunocompetent adult recipients without immunosuppression (79). Neural stem cells were also found to possess inherent immune privilege and resist destruction as allografts (80)
Hence, the study of circulating adult stem cells led us to define transplantation rules for adult stem cells that differ from those of the other cells of the organism. Stem cell grafts need to match the tissue type of the recipient, - not to avoid rejection – which is the usual rule – ,but to allow destruction of the grafted cells in case they accumulate in too great a number in the patient’s tissue (9).
It follows that:
embryonic stem cells that lack expression of class II MHC molecules (81-82) are unable to activate phagic T lymphocytes and then cannot be controlled.
embryonic stem cells derived from cloned embryos are still embryonic stem cells and as such will still lack expression of class II MHC molecules and escape T lymphocyte control.
This is in agreement with recent reports showing that embryonic stem cells transplanted in a fully mismatched recipient are not rejected (6-7). Hence, the reason why therapeutic cloning was proned falls by itself. Despite this, the political debate about therapeutic cloning continues.
From this study of the regulation of adult stem cells present in blood it follows that, from a mere scientific point of view, embryonic stem cells appear very dangerous. Embryonic stem cells either derived from ‘surplus’ embryos or from embryos created by therapeutic cloning, lack surface molecules that allow regulation. Transplantation of such stem unable to be controlled in case of excessive accumulation and with high proliferative potential can lead to fibrosis and/or malignancy. Indeed, the formation of teratocarcinoma has been observed after transplantation of mouse embryonic stem cells (10).
Research should focus on adult stem cells that are specifically designed for tissue repair and which, as such, are tightly controlled. The difficulty is to get them in sufficient quantities. It seems, however, that nature has been generous for the scientific community since the cord blood, a waste product at birth, is appearing to contain a great number of adult stem cells.
Umbilical cord blood: a rich source of adult organ stem cell.
Umbilical cords already used as a rich source of hematopoietic stem cells (83) are now emerging as a new source of organ stem cells.
Umbilical cords and placenta were usually discarded after birth. Collecting cord blood is relatively simple. Immediately after a baby is delivered, the umbilical cord is clamped. The baby is then removed from the area and the placenta is placed in a sterile supporting structure with the umbilical cord hunging through the support. Blood is collected under sterile conditions, by gravity drainage, yielding an average of 75 milliliters of blood. Indeed, stem cells derived from cord blood enter in the category of adult stem cells and their use does not rise any ethical problems.
It is a very young field of research that appears very promising. Human cord blood-derived cells engraft into immunodeficient mice and become mature hepatocytes (84). They also were found able to act as healthy brain cells that showed an affinity for the injured area of the brain. (85)
Cord blood stem cells are found among monocytes (86) and express neural markers (86-87) and the intermediate filament nestin (88). These characteristics are similar to those we reported for stem cells found in adult human blood (8)(67)(71)(73)(76). There is still to check if cord blood stem cells express class II MHC molecules in order to be able to activate and be controlled by phagic T lymphocytes. In vitro studies of stem cells found in adult blood show that this control occurs as soon as the stem cells lose their monocytoid shape, adhere to the support and start differentiating. That probably mimicks what happens in vivo at the interface capillary-tissue. As a consequence, the best way to administer stem cells might be intravenous. Indeed, cord blood stem cells administered intravenously were found able to reduce neurological deficit in the rat after traumatic brain injuries (89-90).
It was mentioned above that in order to allow their regulation organ stem cell grafts need to match the tissue type of the recipient. Tissue-typed allogeneic grafts could be derived from the large potential donor pool of umbilical cords. Facilities that collect and store this product are called cord blood banks. It is necessary to distinguish between public cord blood banks (not-for-profit) designed to provide blood from unrelated donors (allogeneic use) and private (for-profit) facilities that offer storage of cord blood in the event it is needed by the donor infant or family member at a later time (autologous use). Contrarily to private cord blood banks, public cord blood banks do not charge patients for donating cord blood.
Interestingly, stem cells have also been found in umbilical cord mesenchyme that are able to express neural marker when cultured in vitro (91) and when injected into rat brain (92). Stem cells have also been found in human amniotic fluid (93)
CLINICAL USE OF HUMAN ORGAN STEM CELLS
Organs stem cells, particularly bone marrow organ stem cells have already been used with clinical success. The easy access to marrow stem cells, also called mesenchymal stem cells (MSCs) or multipotentent adult progenitor cells (MAPCds) confers on them a great advantage for therapeutic use. Human bone marrow stem cells are relatively easy to propagate (94). Mesenchymal stem cells (MSCs) have been used in 1999, to treat three children with osteogenesis imperfecta (95) (96). Bone marrow stem cells were also found able to repair the infarcted myocardium (97-99). They are also used to engineer cardiovascular tissue, such as cardiac valves and blood vessels (100). An interesting observation seems to indicate that bone marrow stem cells transplantation might have a beneficial effect on Duchenne muscular dystrophy (101).
CONCLUSION
Up to now, embryonic stem cells are laboratory devices, not mastered tools. They are injured cells that have been rendered unable to accomplish their destiny, i.e. to make a baby, They have not yet acquired the hallmark of normal adult stem cells i.e. the ability to be regulated. In the present state of knowledge, it seems premature to speak about potential cure of diseases by using embryonic stem cells. The preliminary experiments necessary to show that they can be controlled, have not been carried out. Recent findings demonstrate that embryonic stem cells transplanted into foreign hosts are not rejected ; that also means that they cannot be controlled.
The rules governing transplantation of embryonic stem cells have not been seriously studied. This work should have been done using mice. It has to be repeated here that Peter Medawar, who was awarded the Nobel Prize in 1958 for discovering the rules governing tissue transplantation, did on mice all his experiments, so useful for mankind.
While the proceedings of this meeting were in press, one of the founding stem cell researchers (102), John Gearhart speaking on 14th November, 2002 at the “Human Embryonic Stem Cells: Differentiation and Transplantation” conference convened by the National Human Genome Research Institute, admitted that embryonic stem cells will not be used for therapy (103). This statement confirms that the ethical and political debate, that started about their therapeutic use, was premature.
So, why such a hurry to directly experiment on human embryos? Indeed companies that support this research are concerned by money and the reports by Thomson (1-2) indicated that human embryonic stem cells could be used for the identification of new drug. But ideology can also be a driving force. Here we have to remember Louis Pasteur. When he discovered microorganisms, he had against him most of the Academy and most of the University who wanted to believe in ‘spontaneous generation’ (104)
Hence, Louis Pasteur’s story told us that utopia does not necessarily open the right tracks leading to scientific truth.
Major efforts should be devoted to better understand stem cells normally present in the adult organism, for repair purposes. Successful adult stem cell therapies imply a full knowledge of the mechanisms regulating these cells. Control by phagic T lymphocytes, described here, is probably only one of them.
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