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

ABSTRACT: Human iPSCs were differentiated into a specific mesoderm subset characterized by KDR+CD56+APLNR+ (KNA+) expression. KNA+ cells possessed high clonal proliferative potential and specification into endothelial colony forming cell (ECFC) phenotype. KNA+ cells differentiated into perfused blood vessels when implanted subcutaneously into the flank of NOD/SCID 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 towards normal healthy retina. These data provide “proof of principle” that KNA+ cells restore perfusion and correct vascular dysfunction in db/db mice.

ORGANISM(S): Homo sapiens

PROVIDER: GSE191206 | GEO | 2021/12/25

REPOSITORIES: GEO

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Expression data from whole retina of 8-week old db/db diabetic mice and lean littermates

Project description:Diabetic retinopathy is one of the leading causes of blindness in diabetic patients. Emerging evidence suggests that retinal neurodegeneration is an early event in the pathogenesis of diabetic retinopathy, but the underlying causes of neuronal loss are unknown. To unravel potential mechanisms underlying early retinal neurodegeneration in diabetic retinopathy, a gene expression profiling study was undertaken to compare the gene expression in retinas of 8-week db/db diabetic mice with that of lean non-diabetic littermates. Retinas were obtained from 8-week db/db diabetic mice and age-matched lean non-diabetic controls. Total RNA was extracted and processed for being hybridized onto affymetrix DNA microarrays.

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Expression data from whole retina of 8-week old db/db diabetic mice and lean littermates

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2016-12-13 | PXD003349 | Pride

Expression analysis in pancreatic and liver tissues of diabetic db/db mice in response to dietary supplementation with selenate

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Transcriptome Alteration in the Diabetic Heart by Rosiglitazone: Implications for Cardiovascular Mortality

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