Modern cell therapy has been around for 100 years, with blood transfusions and the development over the last 50 years of allogeneic hematopoietic stem cell transplants (HSC), skin and cartilage autografts, and anti-infectious and anti-tumor immunotherapy (T and NK lymphocytes).
New advances linked to advances in our knowledge of stem cells are now conceivable - cells with the capacity for self-renewal through asymmetric division. These cells are in fact present in many tissues, but in very different numbers (from bone marrow, intestine and skin - tissues with rapid, continuous renewal - to the brain). A new concept is that, under conditions of aggression, certain cells - at least epithelial cells - are capable of dedifferentiating, i.e. reacquiring stem cell properties, or transdifferentiating, i.e. giving rise to a cell of another lineage. These two processes are particularly involved in the repair (regeneration) of epithelial tissues damaged (by trauma, infection, etc.): this is the case of respiratory (trachea, etc.), digestive (stomach, intestine), hepatic (bile ducts), pancreatic and renal epithelia. Understanding and controlling these processes is likely to open up new avenues in regenerative medicine, which will be discussed below. The second breakthrough concerns the characterization, manipulation and creation of pluripotent stem cells capable of giving rise to cells from the 3 embryonic layers: ectoderm, mesoderm and endoderm. Since 1981, it has been possible to culture (indefinitely) mouse embryonic stem cells derived from the inner mass of the blastocyst. In 1998, J. Thomson characterized the equivalent cells in humans. These embryonic stem (ES) cells represent a potential source for regenerative cell therapy, since they can give rise under precise conditions to cells of (almost) all tissues. Practical limitations include: i) the immunogenicity of ES cells derived from a different individual, ii) the risk of tumors if ES cells persist, and iii) mastery of the in vitro differentiation process in the desired tissue. Two successive methods of creating ES cells have been invented: the first involves transferring the nucleus of a mature cell into the enucleated cytoplasm of a fertilized oocyte. The cellular environment can enable reprogramming of the mature cell's genome into an ES cell. The second, even more spectacular example involves the reprogramming of a mature cell (fibroblast, etc.) into an ES cell by the introduction of 4 transcription factors which alone induce this reprogramming. This is the remarkable result of S. Yamanaka's work. Such cells, known as iPS (for induced pluripotent stem cells), are of great interest: they are ideal models for studying normal and pathological tissue differentiation, and for testing new drugs (pharmacological model); could they be used therapeutically? Their advantage over ES cells is that iPS cells can be derived from the patient himself/herself, thus avoiding the risk of graft rejection, and that their production does not require oocyte donation. On the other hand, their use shares with ES cells the risk of cancer induction and the need to master differentiation procedures (see above). In addition, it is necessary to ensure the "faithful" character of genome reprogramming into pluripotent stem cells, and to consider the risks inherent in the presence of the 4 reprogramming factors (although it is possible to make their presence transient). To date, these questions have not been answered in a sufficiently solid manner to envisage a therapeutic application in the short term.
