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

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 in...

Full description

Saved in:
Bibliographic Details
Published in:Science advances 2022-03, Vol.8 (9), p.eabm5559-eabm5559
Main Authors: Gil, Chang-Hyun, Chakraborty, Dibyendu, Vieira, Cristiano P, Prasain, Nutan, Li Calzi, Sergio, 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
Format: Article
Language:English
Subjects:
Biomedicine and Life Sciences
Cell Biology
Diseases and Disorders
SciAdv r-articles
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 ( 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 mice injected with either control or diabetic donor-derived KNA cells showed correction of aberrant signaling in retinas toward normal healthy retina. These data provide "proof of principle" that KNA cells restore perfusion and correct vascular dysfunction in mice.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.abm5559