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Stem Cells. 2019 Feb 5. doi: 10.1002/stem.2986. [Epub ahead of print]

Functional equivalency in human somatic cell nuclear transfer - derived endothelial cells.

Author information

1
Department of Stem Cell Biology, Konkuk University, School of Medicine, Seoul, Republic of Korea.
2
CHA Stem Cell Institute, CHA University, Seongnam, Republic of Korea.
3
BYON Co. Ltd., Stem Cell Research Center, Seoul, Republic of Korea.
4
Advanced Bio Micro (ABM) Scientific Co. Cheonan, Republic of Korea.
5
Research Institute for Stem Cell Research, CHA Health Systems, Los Angeles, California, USA.
6
Department of Biomedical Science, CHA University, Seongnam, Republic of Korea.
7
Research Institute, T&R Biofab Co. Ltd, 237, Siheung, Republic of Korea.

Abstract

The derivation of human embryonic stem cells (hESCs) by somatic cell nuclear transfer (SCNT) has prompted a re-emerging interest in utilizing 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 (hNT-ESC-EC) transplantation in hindlimb ischemic mice rescued the hindlimb 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. SIGNIFICANCE STATEMENT: Despite recent advancements toward increasing the efficacy of hNT-ESC derivation, the differentiation potential and therapeutic benefits have not been thoroughly investigated. This study demonstrates the cellular function of differentiated hNT-ESCs in an ischemic mice model in comparison to that of IVF-ESCs derived from the embryo of a donor. The derived hNT-ESC-ECs were isolated by sorting for CD31+ expressing cells which exhibited signature endothelial characteristics in vitro such as tubule formation and ac-LDL uptake. While the hNT-ESC-ECs possessed angiogenic potential, its impact on restoring blood perfusion to an ischemic limb was slightly lower than hESC-EC transplantation.

KEYWORDS:

cell therapy; cell transplantation; endothelial cell; human somatic cell nuclear transfer; ischemia

PMID:
30721559
DOI:
10.1002/stem.2986

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