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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.

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


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.


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


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