Human-induced pluripotent stem cells (hiPSCs) cells have the proliferative potential and ability to differentiate into numerous cell types. We have previously generated vascular wall-derived reparative cells called endothelial colony-forming cells (ECFCs) from iPSCs derived from well-characterized, healthy, and diabetic individuals [1]. Our studies showed that these human iPSCs incorporate into blood vessels when implanted subcutaneously into immune compromised mice. These cells, of either diabetic or nondiabetic origin, when injected into the vitreous of diabetic mice with retinal damage, are incorporated into retinal blood vessels and restore perfusion to ischemic areas. Our studies also show that iPSCs from diabetic donors are able to function in vivo and that reprogramed diabetic iPSC cells behave similarly to nondiabetic hiPSCs. The iPSC-derived ECFCs improved the electroretinograms of the diabetic mice and their ocular kinetic responses. These studies support the notion that iPSCs of diabetic and nondiabetic origin, when differentiated into ECFCs, can correct vascular dysfunction, which in turn improves key functions of the neural retina.
Author Contributions
Conceptualization: C.-H.G., D.C., N.P., M.C.Y., M.E.B. and M.B.G.; methodology: C.-H.G., D.C., N.P., K.B., Y.L., H.-M.C., M.C.Y. and M.B.G.; investigation: C.-H.G., D.C., C.P.V., N.P., S.L.C., S.D.F., P.H., C.H., M.S.S., Y.L., X.H., M.D.D., J.L.F., R.P., A.L.F.L., T.J.M., M.E.B., M.J. and D.N.K.; writing—original draft: C.-H.G., D.C., N.P., M.C.Y. and M.B.G.; writing—review and editing: C.-H.G., D.C., D.N.K., M.E.B., M.C.Y. and M.B.G.; funding acquisition: M.E.B., D.N.K., M.P.M., M.C.Y. and M.B.G.; supervision: M.C.Y. and M.B.G. All authors have read and agreed to the published version of the manuscript.
Funding
This research was funded by National Eye Institute (NEI) [EY012601].
Institutional Review Board Statement
IRB-300000173 University of Alabama.
Informed Consent Statement
Not applicable.
Data Availability Statement
Data will be made available upon request.
Conflicts of Interest
M.C.Y. and N.P. are inventors on a pending patent US20190211304A1 related to this work filed by Indiana University Research and Technology Corp (no. 16/323,722, filed 4 August 2017, published 11 July 2019). M.C.Y. is the scientific founder and holds equity in Vascugen Inc., a biotechnology company deriving regenerative medicine cell therapies from iPSCs.
Reference
- Gil, C.-H.; Chakraborty, D.; Vieira, C.P.; Prasain, N.; Calzi, S.L.; Fortmann, S.D.; Hu, P.; Banno, K.; Jamal, M.; Huang, C.; et al. Specific mesoderm subset derived from human pluripotent stem cells ameliorates microvascular pathology in type 2 diabetic mice. Sci Adv. 2022, 8, eabm5559. [Google Scholar] [CrossRef] [PubMed]
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