期刊
SCIENCE ADVANCES
卷 8, 期 9, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abm5559
关键词
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资金
- VSRC core grant [P30 EY003039]
- NIH, National Cancer Institute (NCI) [P30 CA082709]
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [U54 DK106846]
- NIH [1S10D012270, U01TR001810, R01HL095993, N01 75N92020C00005]
- National Heart, Lung, and Blood Institute (NHLBI) [R01HL128827-01]
- NEI [EY012601]
- UAB High Resolution Imaging Facility
- [S10 RR026887]
Human induced pluripotent stem cells (hiPSCs) can differentiate into specific mesoderm cells and restore vascular dysfunction in 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 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.
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