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Biotechnol Bioeng. 2019 Feb;116(2):415-426. doi: 10.1002/bit.26860. Epub 2018 Dec 9.

Assessing the ability of human endothelial cells derived from induced-pluripotent stem cells to form functional microvasculature in vivo.

Author information

1
Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan.
2
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.

Abstract

Forming functional blood vessel networks is a major clinical challenge in the fields of tissue engineering and therapeutic angiogenesis. Cell-based strategies to promote neovascularization have been widely explored, but cell sourcing remains a significant limitation. Induced-pluripotent stem cell-derived endothelial cells (iPSC-ECs) are a promising, potentially autologous, alternative cell source. However, it is unclear whether iPSC-ECs form the same robust microvasculature in vivo documented for other EC sources. In this study, we utilized a well-established in vivo model, in which ECs (iPSC-EC or human umbilical vein endothelial cells [HUVEC]) were coinjected with normal human lung fibroblasts (NHLFs) and a fibrin matrix into the dorsal flank of severe combined immunodeficiency mice to assess their ability to form functional microvasculature. Qualitatively, iPSC-ECs were capable of vessel formation and perfusion and demonstrated similar vessel morphologies to HUVECs. However, quantitatively, iPSC-ECs exhibited a two-fold reduction in vessel density and a three-fold reduction in the number of perfused vessels compared with HUVECs. Further analysis revealed the presence of collagen-IV and α-smooth muscle actin were significantly lower around iPSC-EC/NHLF vasculature than in HUVEC/NHLF implants, suggesting reduced vessel maturity. Collectively, these results demonstrate the need for increased iPSC-EC maturation for clinical translation to be realized.

KEYWORDS:

HUVECs; endothelial cell; iPSCs; vascularization

PMID:
30414271
PMCID:
PMC6322937
[Available on 2020-02-01]
DOI:
10.1002/bit.26860

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