Deskripsi: Basic and Clinical Application of Stem Cell

Induced pluripotent stem (iPS) cells are generated from somatic cell by introducing small sets of transcription factors. Like Embryonic stem (ES) cells, iPS cells can proliferate infinitely and differentiate into various kinds of somatic cells. In addition, unlike ES cells, iPS cells are generated from cells of various characterized donors without destruction of an embryo accompanied by ethical issues. Therefore iPS cells are expected to apply to studies on pathogenesis, drug discovery and cell therapy.

To realize cell therapy using iPS cells, the issues on safeness are the most important. We should control the risks of infection and tumorigenecity, and stability of the quality of the product. For that purpose, we must take heed of several point s unique to cell therapy using iPS cells.

The first, cell therapy using iPS cells consist of a lot of processes and spend long time. Processes for cells and organ transplantation therapy are generally divided into harvesting, processing and transplantation. In iPS-cell therapy, cell processing is very complex and has heavy weight: primary culture of donor cells, generation and expansion of iPS cells, evaluation of undifferentiated iPS cells, differentiation and evaluation of terminal product s. It takes more than a half year for these sequential processes using many kinds of materials. Then, fears of pathogen contamination in the cell processing should be relatively higher. On the other hand, risks of infection from the donor could be relatively lower because long period between harvest and transplantation allows us to do repeated test, e.g. paired serum, for avoiding pseudo-negative results. The risk of genetic or epigenetic abnormality given rise to in the processing should be noted rather than those carried by the donor.

The second, in contrast to embryonic stem cells, which are generated fundamentally one method, there are variations in technologies for generating iPS cells. iPS cells are generated from various origins, by introducing several sets of programming factors with various gene transduction methods. These variations affect quality of iPS cells, so we must establish appropriate method to generate iPS cells for clinical use.

The third, at least so far, there is diversity of qualities even among iPS cells generated with the same methods. Although we someday might establish the method to generate iPS cells with uniform quality, we must establish the strategy for selection of good iPS cell lines at the present time. One of the most important advantages of iPS cells in the quality control of cell-based product s is their ability of infinite proliferation. Once we select a good iPS clone, we can expand the clone unlimitedly, providing enough samples for exhaustive tests. And we can manufacture well-investigated “ good” cells in large lot. We must struggle to clarify what iPS clones should be regarded as “ good” ones, especially in tumorigenecity and function. Non-clinical evaluations of them are not simple. We should discreetly infer the risk for transplanted iPS-derived cells of developing tumor in human recipient s, through both deterministic approaches such as genomics and epigenomics, and stochastic ones such as transplantation assay in animals.

Each approach has both advantages and disadvantages. Well-managed comprehensive evaluations should be required.