Single cell-derived clonally expanded mesenchymal progenitor cells from somatic cell nuclear transfer-derived pluripotent stem cells ameliorate the endometrial function in the uterus of a murine model with Asherman's syndrome

Cell Prolif. 2019 May;52(3):e12597. doi: 10.1111/cpr.12597. Epub 2019 Mar 21.

Abstract

Objectives: 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).

Materials and methods: 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.

Results: 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.

Conclusions: Somatic cell nuclear transfer-derived-hPSCs-MPCs could be an advanced therapeutic strategy for specific diseases in the field of regenerative medicine.

Keywords: Asherman’s Syndrome; angiogenesis; human pluripotent stem cells; mesenchymal progenitor cells; somatic cell nuclear transfer.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cellular Reprogramming Techniques
  • Clone Cells / transplantation
  • Disease Models, Animal
  • Endometrium / pathology
  • Endometrium / physiopathology
  • Female
  • Gynatresia / pathology
  • Gynatresia / physiopathology
  • Gynatresia / therapy*
  • Humans
  • Mesenchymal Stem Cell Transplantation*
  • Mice
  • Mice, Inbred ICR
  • Neovascularization, Physiologic
  • Nuclear Transfer Techniques
  • Pluripotent Stem Cells / transplantation
  • Regenerative Medicine
  • Uterus / pathology
  • Uterus / physiopathology