CHA Advanced Research Institute, Seongnam, Korea.
Department of Biomedical Science, CHA University, Seongnam, Korea.
Cell Prolif. 2019 May;52(3):e12597. doi: 10.1111/cpr.12597. Epub 2019 Mar 21.
Because primary mesenchymal progenitor cells (adult-MPCs) have various functions that depend on the tissue origin and donor, de novo MPCs from human pluripotent stem cells (hPSCs) would be required in regenerative medicine. However, the characteristics and function of MPCs derived from reprogrammed hPSCs have not been well studied. Thus, we show that functional MPCs can be successfully established from a single cell-derived clonal expansion following MPC derivation from somatic cell nuclear transfer-derived (SCNT)-hPSCs, and these cells can serve as therapeutic contributors in an animal model of Asherman's syndrome (AS).
We developed single cell-derived clonal expansion following MPC derivation from SCNT-hPSCs to offer a pure population and a higher biological activity. Additionally, we investigated the therapeutic effects of SCNT-hPSC-MPCs in model mice of Asherman's syndrome (AS), which is characterized by synechiae or fibrosis with endometrial injury.
Their humoral effects in proliferating host cells encouraged angiogenesis and decreased pro-inflammatory factors via a host-dependent mechanism, resulting in reduction in AS. We also addressed that cellular activities such as the cell proliferation and population doubling of SCNT-hPSC-MPCs resemble those of human embryonic stem cell-derived MPCs (hESC-MPCs) and are much higher than those of adult-MPCs.
Somatic cell nuclear transfer-derived-hPSCs-MPCs could be an advanced therapeutic strategy for specific diseases in the field of regenerative medicine.
由于原代间充质祖细胞(成人-MPCs)具有依赖组织起源和供体的多种功能,因此在再生医学中需要来自人类多能干细胞(hPSCs)的新的 MPCs。然而,来自重编程 hPSCs 的 MPC 的特征和功能尚未得到很好的研究。因此,我们表明,源自体细胞核转移衍生的 hPSCs(SCNT-hPSCs)的 MPC 衍生的单细胞克隆扩增可以成功建立功能性 MPCs,并且这些细胞可以作为 Asherman 综合征(AS)动物模型中的治疗贡献者。
我们开发了源自 SCNT-hPSCs 的 MPC 衍生的单细胞克隆扩增,以提供纯群体和更高的生物学活性。此外,我们研究了 SCNT-hPSC-MPC 在 Asherman 综合征(AS)模型小鼠中的治疗效果,AS 的特征是粘连或纤维化伴有子宫内膜损伤。
它们在增殖宿主细胞中的体液作用通过宿主依赖性机制促进血管生成并减少促炎因子,从而减少 AS。我们还解决了 SCNT-hPSC-MPC 的细胞活性,如细胞增殖和群体倍增,类似于人胚胎干细胞衍生的 MPC(hESC-MPCs),并且远高于成人-MPCs。
源自体细胞核转移衍生的 hPSCs-MPC 可能是再生医学领域特定疾病的先进治疗策略。