Specific mesoderm subset derived from human pluripotent stem cells ameliorates microvascular pathology in type 2 diabetic mice Journal Article

   


Authors: Gil, C. H.; Chakraborty, D.; Vieira, C. P.; Prasain, N.; Calzi, S. L.; Fortmann, S. D.; Hu, P.; Banno, K.; Jamal, M.; Huang, C.; Sielski, M. S.; Lin, Y.; Huang, X.; Dupont, M. D.; Floyd, J. L.; Prasad, R.; Longhini, A. L. F.; McGill, T. J.; Chung, H. M.; Murphy, M. P.; Kotton, D. N.; Boulton, M. E.; Yoder, M. C.; Grant, M. B.
Article Title: Specific mesoderm subset derived from human pluripotent stem cells ameliorates microvascular pathology in type 2 diabetic mice
Abstract: 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. Copyright © 2022 The Authors.
Keywords: cytology; gene expression; stem cells; pluripotent stem cells; mammals; clone cells; blood vessels; cell signaling; cell phenotype; microvascular; human-induced pluripotent stem cells; diabetic mice; cell-be; cell/b.e; cell/be; db/db mouse; endothelial colony forming cells
Journal Title: Science Advances
Volume: 8
Issue: 9
ISSN: 2375-2548
Publisher: Amer Assoc Advancement Science  
Date Published: 2022-03-04
Start Page: eabm5559
Language: English
DOI: 10.1126/sciadv.abm5559
PUBMED: 35245116
PROVIDER: scopus
PMCID: PMC8896785
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85125774007&doi=10.1126%2fsciadv.abm5559&partnerID=40&md5=798e3c643b8f7b8657591a975c0991db
Notes: Article -- Export Date: 1 April 2022 -- Source: Scopus
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MSK Authors
  1. Ana Leda Figueiredo Longhini
    9 Figueiredo Longhini
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