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

• Published in: Stem cells (Dayton, Ohio) Ohio), 2019-05, Vol.37 (5), p.623-630
• Main Authors: Park, Soon‐Jung, Lee, Ji‐Heon, Lee, Seul‐Gi, Lee, Jeoung Eun, Seo, Joseph, Choi, Jong Jin, Jung, Taek‐Hee, Chung, Eun‐Bin, Kim, Ha Na, Ju, Jongil, Song, Yun‐Ho, Chung, Hyung‐Min, Lee, Dong Ryul, Moon, Sung‐Hwan
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation - genetics; Cell lines; Cell therapy; Cell transplantation; Cloning; Derivation; Differentiation; Embryo cells; Embryos; Endothelial cell; Endothelial cells; Endothelial Cells - transplantation; Equivalence; Hindlimb - pathology; Hindlimb - transplantation; Human behavior; Human Embryonic Stem Cells - transplantation; Human somatic cell nuclear transfer; Humans; Induced Pluripotent Stem Cells - transplantation; Ischemia; Ischemia - therapy; Low density lipoprotein; Mice; Mitochondrial DNA; Morphology; Neurotrophin 4; Nuclear transfer; Nuclear Transfer Techniques; Perfusion; Physical characteristics; Pluripotency; Somatic cell nuclear transfer; Stem cell transplantation; Stem cells; Transplantation
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1002/stem.2986

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 NT‐ESC derived ECs through a concave microwell system demonstrates functional potential regarding the restoration of blood perfusion to an ischemic limb through angiogenic factors.