For an extended period of time, research on human embryo implantation and early placentation was hindered by ethical limitation and lack of appropriate in vitro models. Recently, an explosion of new research has significantly expanded our knowledge of early human trophoblast development and facilitated the derivation and culture of self-renewing human trophoblast stem cells (hTSCs). Multiple approaches have been undertaken in efforts to derive and understand hTSCs, including from blastocysts, early trophoblast tissue, and, more recently, from human pluripotent stem cells (hPSCs) and somatic cells. In this concise review, we summarize recent advances in derivation of hTSCs, with a focus on derivation from naive and primed hPSCs, as well as via reprogramming of somatic cells into induced hTSCs. Each of these methods harbors distinct advantages and setbacks, which are discussed. Finally, we briefly explore the possibility of the existence of trophectoderm-like hTSCs corresponding to earlier, preimplantation trophoblast cells.
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