Browsing by Author "Kotton, Darrell N."

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    Specific mesoderm subset derived from human pluripotent stem cells ameliorates microvascular pathology in type 2 diabetic mice
    (American Association for the Advancement of Science, 2022) Gil, Chang-Hyun; Chakraborty, Dibyendu; Vieira, Cristiano P.; Prasain, Nutan; Calzi, Sergio Li; Fortmann, Seth D.; Hu, Ping; Banno, Kimihiko; Jamal, Mohamed; Huang, Chao; Sielski, Micheli S.; Lin, Yang; Huang, Xinxin; Dupont, Mariana D.; Floyd, Jason L.; Prasad, Ram; Longhini, Ana Leda F.; McGill, Trevor J.; Chung, Hyung-Min; Murphy, Michael P.; Kotton, Darrell N.; Boulton, Michael E.; Yoder, Mervin C.; Grant, Maria B.; Pediatrics, School of Medicine
    Human induced pluripotent stem cells (hiPSCs) were differentiated into a specific mesoderm subset characterized by KDR+CD56+APLNR+ (KNA+) expression. KNA+ cells had high clonal proliferative potential and specification into endothelial colony-forming cell (ECFCs) phenotype. KNA+ cells differentiated into perfused blood vessels when implanted subcutaneously into the flank of nonobese diabetic/severe combined immunodeficient mice and when injected into the vitreous of type 2 diabetic mice (db/db mice). Transcriptomic analysis showed that differentiation of hiPSCs derived from diabetics into KNA+ cells was sufficient to change baseline differences in gene expression caused by the diabetic status and reprogram diabetic cells to a pattern similar to KNA+ cells derived from nondiabetic hiPSCs. Proteomic array studies performed on retinas of db/db mice injected with either control or diabetic donor-derived KNA+ cells showed correction of aberrant signaling in db/db retinas toward normal healthy retina. These data provide "proof of principle" that KNA+ cells restore perfusion and correct vascular dysfunction in db/db mice.