Functional Equivalency in Human Somatic Cell Nuclear Transfer-Derived Endothelial Cells

Stem Cells. 2019 May;37(5):623-630. doi: 10.1002/stem.2986. Epub 2019 Feb 22.

Abstract

The derivation of human embryonic stem cells (hESCs) by somatic cell nuclear transfer (SCNT) has prompted a re-emerging interest in using such cells for therapeutic cloning. Despite recent advancements in derivation protocols, the functional potential of CHA-NT4 derived cells is yet to be elucidated. For this reason, this study sought to differentiate CHA-NT4 cells toward an endothelial lineage in order to evaluate in vitro and in vivo functionality. To initial differentiation, embryoid body formation of CHA-NT4 was mediated by concave microwell system which was optimized for hESC-endothelial cell (EC) differentiation. The isolated CD31+ cells exhibited hallmark endothelial characteristics in terms of morphology, tubule formation, and ac-LDL uptake. Furthermore, CHA-NT4-derived EC (human nuclear transfer [hNT]-ESC-EC) transplantation in hind limb ischemic mice rescued the hind limb and restored blood perfusion. These findings suggest that hNT-ESC-EC are functionally equivalent to hESC-ECs, warranting further study of CHA-NT4 derivatives in comparison to other well established pluripotent stem cell lines. This revival of human SCNT-ESC research may lead to interesting insights into cellular behavior in relation to donor profile, mitochondrial DNA, and oocyte quality. Stem Cells 2019;37:623-630.

Keywords: Cell therapy; Cell transplantation; Endothelial cell; Human somatic cell nuclear transfer; Ischemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Endothelial Cells / transplantation*
  • Hindlimb / pathology
  • Hindlimb / transplantation
  • Human Embryonic Stem Cells / transplantation*
  • Humans
  • Induced Pluripotent Stem Cells / transplantation*
  • Ischemia / therapy
  • Mice
  • Nuclear Transfer Techniques