STEM CELLS AND THE MYTH OF ETERNAL YOUTH: ADULT VERSUS EMBRYONIC STEM CELLSDr. Marie - Louise Labat
The myth of eternal youth has always haunted humanity. Today, what is at stake is regenerative medicine using stem cells.
Stem cells are undifferentiated cells that given the right signals can differentiate to the many (more than 200) specialized cells that make up the organism. Stem cells have the ability to self-replicate for the lifetime of the organism.
Different types of stem cells are involved during human development and adult life.
HUMAN DEVELOPMENTAL CONTINUUM Fetus Totipotent Stem Cells Pluri/ Multi potent Embryonic germ (EG) cells Pluripotent Tissue stem cells Pluripotent/Multipotent Pluripotent Adapted from David Prentice
Distinguishing Features of Progenitor/Precursors Cells and Stem Cells. http://stemcells.nih.gov/info/scireport/chapter4.pdf
Human embryo at stage 8 cells (2 days) 8 totipotent stem cells
Inner Mass Human embryo at blastocyst stage 200-250 cells (4 to 5 days) (Pluripotent stem cells)
From G. Baker: http://www.city.ac.uk/cs/lecturenotes/neuro_biomedsciences.pdf
Then, gastrulation leads to the establishment of definitive germ layers (ectoderm, endoderm, and mesoderm) that harbour multipotent cells.
From Human Embryology, Larsen, DeBoeck University Ed, Bruxelles, Belgium, 1996
According to the classical dogma, pluripotency was thought to be lost after the blastocyst stage.
Therefore, so-called pluripotent embryonnic stem cells are extracted before gastrulation, from the inner mass of the blastocyst From ‘Science et Avenir’ 2002, n° 130, special issue
Martin G;Isolation of pluripotent cell lines from early mouse embryos.Proc Natl Acad Sci USA 1981; 78: 7634-7838.
Thomson JA, Istkovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergel JJ, Marshall VS, Jones JM.Embryonic stem cell lines derived from the human blastocyst.Science 1998; 282: 1145-1147
The authors concluded that such human embryonic stem cells could be used for transplantation medicine, in order to cure: - Alzheimer’s disease- Parkinson’s disease- Juvenile type diabetes- Spinal cord injury
However, because extraction of the stem cells from the blastocysts leads to the destruction of a human embryo, a worldwide debate both ethical and political started.
From the time that the ovum is fertilized, a life is begun that 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 become human, if it were not human already.John-Paul II (Evangelium vitae)
The study by Thomson’s team was made using ‘supernumerary embryos’ donated by the parents after informed consent and after institutional review board approval.
But the question is: Whom do these embryos belong to, if not to themselves?
At an April 2002 press conference, Senator A. Specter (Penn) 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. »
First of all, their isolation is the direct consequence of in vitro fertilization and preimplantation diagnosis.
Pipet One cells is taken In vitro culture One cell is sampled from each embryo fertilized and cultured in vitro Embryo between 6 to 12 cells Diagnostic test on each sampled cell Healthy embryos are selected for implantation in the uterus In vitro fertilized ovocyte Preimplantation genetic diagnosis Sciences et Avenir, 2002; 130, Hors-série
1978: birth of the first baby by in vitro fertilization (IVF) in Great Britain. • 1982: birth of a baby by in vitro fertilization in France. • During the past 20 years, 100 000 babies were born in France by IVF. In 1998, more than 13 000 babies were born by IVF (1,8% of birth). This number is in constant increase, due to: • 1. greater efficiency of ovary stimulation, • 2. cryopreservation of embryos.
As a result, the human embryo became available for experimentation.
Human embryo (3 days old, 16 cells) Science et Avenir 2002; 130 Special issue
In fact, embryonic stem cells, at the heart of the present debate are not present as such in the embryo, they result from manipulations in the laboratory.
The pluripotent cells extracted from the inner mass of the blastocyst are manipulated in the laboratory to give rise to cell lines that proliferate indefinitely Science et Avenir 2002, n°130, special issue
Manipulation of embryonic stem cells in the laboratory
- After dissociation of the inner mass of human blastocysts, the cells are first grown on a feeder layer of irradiated mouse embryonic fibroblasts,- after 9 to 15 days of culture, the outgrowth are harvested and replated,- cell lines are selected by their prolonged undifferentiated proliferation characteristics while retaining the ability to differentiate into the three embryonic germ-layers.
Human embryonic stem cell lines approved by President Bush for federally funded research (August 9, 2001) . CyThera (California) 9 • ES Cell International (Australia) 6 • Geron Corporation (California) 7 • University of Göteborg (Sweden) 19 • Maria Biotech Co (Korea) 3 • Miz Medi Hospital (Korea) 1 • National Center for Biological Science (India) 3 • Pochon CHA University (Korea) 2 • Reliance Life Sciences, Bombay (India) 7 • Technion University, Haifa (Israel) 4 • University of California SF (California) 2 • Wisconsin Alumni Research Foundation 5 • Bresagen, Inc (Georgia, USA) 4
These cells lines, created for possible future disease treatments were grown on mouse fibroblasts. That could expose humans to animal virus their immune system couldn’t fight, the U.S. medical ethics panel said on November 2003.
Attempts are made to grow human embryonic stem cell lines without using a feeder layer of mouse fibroblasts and without using fetal calf serum Amit M, Shariki C, Margulets V, Itskovitz-Eldor JFeeder and serum-free culture of human embryonic stem cells.Biol Reprod 2004; 70: 837-45
According to the US National Institutes of Health (NIH), only 11 cell lines can really be considered (some were discarded because contaminated by viruses, or cross-contaminated, or because they were not really stem cells, or for ethical reasons).
One of these cells lines, that had received the agreement of the NIH, that was considered as stable and devoid of chromosome abnormalities was used as a reference. It was widely distributed in 150 laboratories all around the world. This reference cell line was recently shown by Draper and Smith, to be instable and to present an excess of chromosome 12 and 17.
Draper JS, Smith K, et alRecurrent gain of chromosome 17 q and 12 in cultured human embryonic stem cells.Nat Biotechnol 2004; 22: 53-54
108th congress of Office of Legislative Policy and AnalysisRonald McKay National Institute of Neurological Disorders and StrokeMay 22, 2003« There is clear evidence that human ES cells will form teratomas, complex mixtures of different cells, but much less is known about efficiently generating specific cell type … »
In fact, it is difficult to differentiate embryonic stem cells toward one direction only:Schuldiner M, Yanuka O, Itskovitz-Taylor J et al.Effect of eight growth factors on the differentiation of cells derived from human embryonic stem cells.Proc Natl Acad Sci 2000; 97: 11307
Even the pioneer of human embryonic stem cell research, J. A. Thomson, does not believe any more in the therapeutic use of human embryonic stem cells.
In december 1998, J. A. Thomson testified before the American Senate that human embryonic stem cells were going to cure: - Alzheimer’s disease- Parkinson’s disease- Juvenile type diabetes- Spinal cord lesions
On June 2002, J. D. Thomson stated at the « Workshop on the Basic Biology of Mammalian Stem Cells » organized by the National Institute of General Medical Sciences :‘in the next decade, relatively few clinical trials in « cell therapy » will be initiated with human embryonic stem cells, due to safety concerns and possible immune interference …Forecasting that stem cells would have a greater impact on understanding the roots of disease rather than on treatment’
Indeed, that last proposition: ‘…stem cells would have a greater impact on understanding the roots of disease rather than on treatment’could not have motivated the associations of patients to back research on human embryonic stem cells.
A similar evolution can be noted in the statements of the other pionnier J. Gearhardt who derived in 1998 pluripotent cell lines from germ cells from human embryos.
November 19, 2002, J. Gearhart stated in the Washington Fax, the official press organ of the National Institutes of Health:« Embryonic and fetal stem cells likely will never be used as part of disease therapy, but research into both embryonic and fetal stem cells is critical and will provide scientists with vital informations that will enable treatments.
However, the worlwide ethical and political debate continues without taking into account these new informations.Most of the politicians are convinced that embryonic stem cells are, for sure, going to cure Alzheimer’s disease, diabetes, Parkinson’s disease, etc. …
« Research …if conducted in a true scientific way and if it respects moral law , cannot be in conflict with faith. »John-Paul II (Gaudium et spes, n 36)