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

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. K E Y W O R D S endothelial cell, HUVECs, iPSCs, vascularization

Coadministration of endothelial and smooth muscle cells derived from human induced pluripotent stem cells as a therapy for critical limb ischemia

“…15 Coinjection of iPSC-EC with normal human lung fibroblasts and a fibrin matrix into the dorsal flank of severe combined immunodeficiency mice led to the formation of functional microvasculature in vivo. 33 The potential of EC and SMC derived from human iPSC for clinical application in PAD needs to be explored further.…”

The Role of Angiogenesis and Pro-Angiogenic Exosomes in Regenerative Dentistry

“…In a recent study, the endothelial cells were reprogrammed to iPSCs. In comparison to the mature endothelial cells, the iPSCs from endothelial tissue were less capable of forming mature blood vessels and the density of these blood vessels was lower [79]. Even if the iPSCs have the advantage of being an inexhaustible pool of stem cells, these cells are proposed as a regenerative tool to a far lesser extent, because they can often suffer a number of genetic mutation and can give rise to cancer [80].…”

Human iPSC‐derived endothelial cells promote CNS remyelination via BDNF and mTORC1 pathway

“…The discrepancy may arise from experimental settings such as species, age of ECs, and co‐culture time (6 days vs. 2 days). The iPSC‐ECs, with more pre‐maturation characteristics (Bezenah et al, 2019; Jang et al, 2019), are expected to resemble more nascent, less specialized ECs which may have more potent effects on oligodendrocyte lineage progression compared to mature ECs. Although the proportion of the proliferating OPCs is higher in early stage (6 dpl) in lesion, the proportion of the differentiated oligodendrocytes across the whole lineage cells at later stage (11 dpl) was not reflecting the increase found in vitro .…”