A novel lineage restricted, pericyte-like cell line isolated from human embryonic stem cells.
Pericytes (PCs) are endothelium-associated cells that play an important role in normal vascular function and maintenance. We developed a method comparable to GMP quality protocols for deriving self-renewing perivascular progenitors from the human embryonic stem cell (hESC), line ESI-017. We identified a highly scalable, perivascular progenitor cell line that we termed PC-A, which expressed surface markers common to mesenchymal stromal cells. PC-A cells were not osteogenic or adipogenic under standard differentiation conditions and showed minimal angiogenic support function in vitro. PC-A cells were capable of further differentiation to perivascular progenitors with limited differentiation capacity, having osteogenic potential (PC-O) or angiogenic support function (PC-M), while lacking adipogenic potential. Importantly, PC-M cells expressed surface markers associated with pericytes. Moreover, PC-M cells had pericyte-like functionality being capable of co-localizing with human umbilical vein endothelial cells (HUVECs) and enhancing tube stability up to 6 days in vitro. We have thus identified a self-renewing perivascular progenitor cell line that lacks osteogenic, adipogenic and angiogenic potential but is capable of differentiation toward progenitor cell lines with either osteogenic potential or pericyte-like angiogenic function. The hESC-derived perivascular progenitors described here have potential applications in vascular research, drug development and cell therapy.
ReCyte Therapeutics, Inc., Alameda, CA 94501, USA.
Midori
M
Greenwood-Goodwin
StemCells, Inc., Newark, CA 94560, USA.
Jiwei
J
Yang
ReCyte Therapeutics, Inc., Alameda, CA 94501, USA.
Mohammad
M
Hassanipour
ReCyte Therapeutics, Inc., Alameda, CA 94501, USA.
David
D
Larocca
D051929:CD146 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D000066673:Cell Self Renewal; D064987:Cell- and Tissue-Based Therapy; D055808:Drug Discovery; D053595:Embryonic Stem Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D018919:Neovascularization, Physiologic; D010012:Osteogenesis; D020286:Pericytes / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*
D051929:CD146 Antigen