Human Pluripotent Stem Cell-Derived Multipotent Vascular Progenitors of the Mesothelium Lineage Have Utility in Tissue Engineering and Repair

Abstract

SUMMARY In this report we describe a human pluripotent stem cell-derived vascular progenitor (MesoT) cell of the mesothelium lineage. MesoT cells are multipotent and generate smooth muscle cells, endothelial cells, and pericytes and self-assemble into vessel-like networks in vitro. MesoT cells transplanted into mechanically damaged neonatal mouse heart migrate into the injured tissue and contribute to nascent coronary vessels in the repair zone. When seeded onto decellularized vascular scaffolds, MesoT cells differentiate into the major vascular lineages and self-assemble into vasculature capable of supporting peripheral blood flow following transplantation. These findings demonstrate in vivo functionality and the potential utility of MesoT cells in vascular engineering applications.

ROR1-CAR T cells are effective against lung and breast cancer in advanced microphysiologic 3D tumor models

“…The BioVaSc was originally designed for the generation of artificial normal human tissues in regenerative medicine. Several normal human tissues, including trachea, myocardium, liver, skin, intestine, and kidney, have been generated on this platform (12,(35)(36)(37)(38)(39)(40). Accordingly, we believe that there is a potential for assessing safety and tissue cross-reactivity of CAR T cells in 3D normal tissue models.…”

Engineering Brain-Specific Pericytes from Human Pluripotent Stem Cells

“…An alternative approach for mesoderm induction is to generate the multipotent vascular progenitor (MesoT) cells from hPSCs, which can give rise to SMCs, endothelial cells, and PCs, which can self-assemble into vessel-like networks in vitro. 112,113 The differentiation is induced using Wnt3a and BMP4 along with retinoic acid for further differentiation into MesoT cells. The differentiation of MesoT cells to SMCs or endothelial cells was promoted by PDGF-BB or with a combination of VEGF and SB431542, respectively.…”

Generation and characterization of cardiac valve endothelial-like cells from human pluripotent stem cells

“…It is widely accepted that the mammalian embryonic heart is primarily originated from cardiac progenitor cells (CPCs) expressing marker genes such as ISL1, NKX2.5 and KDR (Hinton and Yutzey, 2011;Lui et al, 2013;Misfeldt et al, 2009;Morreti et al, 2006). We and several other groups have previously generated the CPCs from hPSCs (Berger et al, 2016;Colunga et al, 2019;Lyer et al, 2015;Nakano et al, 2016;Patsch et al, 2016;Sahara et al, 2014;Sriram et al, 2015;Tan et al, 2013;White et al, 2013). The common theme of the various differentiation protocols is the activation of WNT and BMP signaling pathways, which mimics the signaling requirement during early specification of heart mesoderm (Ansersen et al, 2018;Nakano et al, 2016;Puceat, 2013).…”

“…Human PSCs including human induced pluripotent stem cells (Colunga et al, 2019) and PGP1 human induced pluripotent stem cells (kindly provided by Prof. Zhang from Hubei University, Wuhan, China), and human ESC lines (H8 and H9 lines, Wicell, WI, USA) were used for this study.…”