Direct reprogramming to multipotent trophoblast stem cells, and is pluripotency needed for regenerative medicine either?

For the clinical applications of regenerative medicine, induced pluripotent stem cells (iPSCs) (all acronyms are defined in the Glossary at the end of the text) have advantages over embryonic stem cells (ESCs) in histocompatibility and the lack of reliance on embryo derivation. Induction of pluripotency can be achieved by transiently expressing a minimal set of transcription factors (TFs) to reprogram differentiated cells. Direct reprogramming of somatic cells into progenitor stem or other mature cells would eliminate the need to make iPSCs, and then direct differentiation and select the desired lineage. Another advantage of direct reprogramming is that by avoiding the pluripotent step, one mitigates the risk of tumorigenicity. Direct reprogramming requires knowledge of the reprogramming factors and knowledge of the culture conditions necessary to maintain the induced multipotent stem cells. The culture conditions for mouse trophoblast stem cells (TSCs) were defined in the 1990s (1,2). Knowledge of how to reprogram mouse fibroblast cells to multipotent TSC has now been provided by two recent publications from the Buganim (3) and the Schorle labs (4). These studies inform not only regenerative medicine but will also aid our understanding of normal and pathological placental development in early pregnancy.