Ever since former U.S. President Bush approved in 2001 federal funding for human embryonic stem cell research, (but then he decided against), the flow of information about this field has enormously increased, and the expectation of public that such research will lead to the therapeutic use of stem cell transplantation for patients with serious diseases has heightened.
On November 2, 2004, a Proposition 71′ passed by voters of the State of California, whereby a $3 billion state fund for stem cell research was created, took the matter of stem cell transplantation from the hands of federal government. A growing number of States have followed the example of California.
Despite steady flow of data media have forgotten to mention that:
- embryonic stem cells are unusable for an actual patient treatment – due to their oncogenicity (capability of inducing tumor) – the fact that has been known for several decades;
- an implantation of fetal precursor (or progenitor) cells – a few generations older than embryonic cells – have been used as a treatment for 80+ years, albeit under different names, so much so that ~ 1 million patients have been so treated in various western countries;
- fetal precursor cells of animal fetal origin are equally effective, and safe, for the patient treatment as those of human fetal origin, so that all difficulties with human embryonic stem cells can be avoided;
- human embryonic stem cells cannot survive in laboratory conditions except by being grown on a ‘feeder’ layer of mouse cells, for which reason U.S. FDA classifies them as ‘Xeno-transplants’, i.e. of animal origin.
Human embryonic cell research must continue, because our knowledge of what happens at the very beginning of human life has been precariously low, particularly on a molecular or genetic level. But many problems associated with the use of human embryonic and fetal cells in medicine should not block precursor cell transplantation of animal fetal origin from helping patients suffering from serious incurable or untreatable diseases.
Therapeutic use of precursor cell transplantation of animal fetal origin in ~ 1 million patients over 85 years has accumulated sufficient data to assure majority of public that this treatment is not dangerous to an individual or to mankind. The above number of 1 million patients represents over 99% of all patients that have received cell transplants to-date. When you place side-by-side human and animal embryonic stem cells, or human and animal fetal precursor cells, of the same type, you would find out that they look alike and even most of the available cell-surface markers are the same.
The only way to tell the cells of one species from another is by their karyotype, the number and shape of chromosomes, the temporary structures created from the genetic material of each cell during one short phase of the cell division cycle.
Embryonic Cell has unique capability to renew itself, i.e. to proliferate, and is pluripotent which means that it has the potential to differentiate into any & all specialized cell type of the body, with a characteristic shape and function of a particular tissue. It remains in an undifferentiated state, i.e. uncommitted, until it gets a signal to develop into one of the specialized cells of the body.
A puzzling problem is that embryonic stem cells apparently do not exist in real life, i.e. in a living embryo, only in the laboratory dish.
The optimism about embryonic stem cells is based on:
- their enormous ability to proliferate which would make them suitable for a factory level manufacturing of cells for therapeutic use; and
- their capability to be manipulated so that they differentiate into any desired cell type to be used for treatment of patients by transplantation.
The unlimited potential of embryonic cells to proliferate sounds wonderful, but only until one comprehends that the same happens in cancer growth: one kind of cell stops responding to the commands of the patient’s body, becomes independent, and decides to become a ‘cell factory’.
A manipulation of embryonic cells into differentiation, whereby precursors/progenitors of any & all specialized cells of the body are created in a laboratory dish, is formidable task as well, presently beyond possibility of solution. But since even fetal precursor cells cannot create in laboratory conditions a three-dimensional body, or an organ, or even a tissue, the question arises whether these cells grown in a laboratory dish are indeed the same precursor cells that can be obtained from a fetus, where they have developed in a natural way.
The kind of cellular and non-cellular environment in which cells are growing (i.e. either tissue culture or live human & animal body) makes a lot of difference when it comes to his direction of cell differentiation.
Let’s Now Focus On Fetal Precursor Cells
When the precursor cells are taken from fetus that already reached the stage of organogenesis, after their implantation in the patient’s body such cells will
- no longer be pluripotential
- be committed to follow a predetermined path of differentiation along one lineage only, i.e. such cells will produce cell type specific for the kind of tissue where these stem cells normally reside
- follow the body commands
- retain the ability to proliferate without differentiating for a long time
This is because in fetal body the undifferentiated stem cells live in milieu of various specialized (differentiated) cells, and there is a lot of interaction between them, while the same is not the case when undifferentiated stem cells grow in tissue culture.
It appears more physiological to us to take precursor cells for transplantation from their natural environment, (i.e. fetus), that means taking them
- along with other cells of the same ‘family';
- in a cell-to-cell contact with cells of the same ‘family';
- along with cells of various generations of the same ‘family';
- then grow them in a primary tissue culture in order to have time for observation and safety tests; as well as
- to lower their immunogenicity so that they can be implanted in a patient without immunosuppressant
All of the above statements apply primarily to the precursor cells obtained from fetuses, not from adults.
Adult organism contains sufficient quantity of stem cells without which the regeneration and continuation of life would not be possible. But adult stem cells have very low therapeutic potential, despite their apparent ability of long-term self-renewal, and of differentiation along a predetermined cell lineage, giving rise to just one cell type for the purpose of maintenance of homeostasis. Most importantly they are as old as the body they originate from and cannot match the vitality of stem cells from fetus.
- Stem cells obtained from fetus are much more numerous than rare adult stem cells and they possess some unique properties, such as: Ability to differentiate and undergo changes in response to environmental stimuli, or in accordance with own genetic make-up;
- Easy adaptability, caused by the plasticity of tissues (and that includes growth, migration, mobility, ability to create cell-to-cell contacts), that in course of normal fetal development gradually decreases, and finally disappears at the completion of development;
- More frequent and faster cell division, and proliferation, as compared with adult cells, depending upon the type of tissue and stage of fetal development;
- Production of large amounts of various biological substances, i.e. growth factors, etc., which facilitate the survival and growth of cells after implantation, and stimulate damaged cells of the host;
- Lowered immunogenicity, that results in a much weaker immune response of the host, as compared when mature cells & tissues are implanted;
- Capability to survive on energy supplied by glycolysis alone and thus lesser amount of oxygen that is important during the preparation of cell transplants and during the first hours after implantation.