Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer

Abstract

SUMMARY Reprogramming somatic cells into pluripotent embryonic stem cells (ESCs) by somatic cell nuclear transfer (SCNT) has been envisioned as an approach for generating patient-matched nuclear transfer (NT)-ESCs for studies of disease mechanisms and for developing specific therapies. Past attempts to produce human NT-ESCs have failed secondary to early embryonic arrest of SCNT embryos. Here, we identified premature exit from meiosis in human oocytes and suboptimal activation as key factors that are responsible for these outcomes. Optimized SCNT approaches designed to circumvent these limitations allowed derivation of human NT-ESCs. When applied to premium quality human oocytes, NT-ESC lines were derived from as few as two oocytes. NT-ESCs displayed normal diploid karyotypes and inherited their nuclear genome exclusively from parental somatic cells. Gene expression and differentiation profiles in human NT-ESCs were similar to embryo-derived ESCs, suggesting efficient reprogramming of somatic cells to a pluripotent state.

Dopaminergic Differentiation of Human Embryonic Stem Cells on PA6-Derived Adipocytes

“…With the recent findings of somatic cell nuclear transfer in humans, human embryonic stem cells (hESCs) become a promising "personalized" source of cells for regenerative medicine [1]. During the past decade, several groups have established various methods for differentiating hESCs into dopaminergic (DAergic) neurons [2][3][4][5].…”

Present and future challenges of induced pluripotent stem cells

“…Recently, the invention of human somatic cell nuclear transfer (SCNT)-ESCs has been reported [78][79][80], and the comparison of gene expressions, epigenetic statuses and genetic alterations between isogenic human SCNT-ESCs and iPSCs derived from the same somatic cell cultures has been discussed [81,82]. Ma et al concluded that iPSCs have inherent abnormalities, because the similarity of SCNTESCs to ESCs derived from in vitro fertilized eggs is greater than that of iPSCs [82].…”

Stem cells and the evolving notion of cellular identity

“…Indeed, SCNT together with directed differentiation of murine ESCs represents a classical paradigm for customized gene and cell therapy to treat genetic disease, as has been shown in murine models [10]. While nuclear transfer has ultimately succeeded in humans [11], it has proven quite cumbersome, requiring harvesting of fresh oocytes from women willing to donate to research.…”