iPS cells : quality controls and validation to become a cell product

Human embryonic stem cells (hESCs) provide new resources for the biomedical community by virtue of their dual capacities: long-term self-renewal and production of differentiated progeny. hESCs may constitute an endless source of cells for the treatment of debilitating diseases and degenerative disorders. In the last few years alternatives to hESCs have been generated, the ”induced pluripotent stem cells” (iPS) which can repro-gram their adult somatic fate to acquire an embryonic-like feature thanks to the ectopic over-expression of four transcription factors (OCT-4, SOX-2, KL44 and c-MYC). iPS cells nowadays represent the biggest expectation for the emerging molecular stem cell medicine branch, although they are not as versatile as the hESCs, but much still needs to be learned of their characteristics and capacities. These cells retain their own genome and an imprint or un-erasable memory of their somatic cellular origin and whatever has occurred in the organ from which they originate. It is then of paramount importance to invest on “methyloma” or methylation profiles of these cells in order to identify their memory stick. Since the number of iPS lines will steadily increase, to become an accreditable cell product, they must be submitted to a number of quality control tests to assure that they are morphologically and biochemically undistinguishable from ESCs. Particularly it is essential to analyze the reactivation of the appropriate stage-specific embryonic antigens, the capacity to differentiate into lineages from all three embryonic germ layers, the teratomas formation in immunodeficient mice, the expression of functional telomerase, the epigenetic status and the transcriptionally permissive chromatin structure of pluripotent genes. iPS should be evaluated by integrative genome-wide approaches, allowing the supervising of pluripotency, or the eventual DNA damage subsequent to the reprogramming.