| Title: |
Specific mesoderm subset derived from human pluripotent stem cells ameliorates microvascular pathology in type 2 diabetic mice |
| Authors: |
Gil, Chang-Hyun; Chakraborty, Dibyendu; Vieira, Cristiano P.; Prasain, Nutan; Calzi, Sergio Li; 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. |
| Contributors: |
Pediatrics, School of Medicine |
| Source: |
PMC |
| Publisher Information: |
American Association for the Advancement of Science |
| Publication Year: |
2022 |
| Collection: |
Indiana University - Purdue University Indianapolis: IUPUI Scholar Works |
| Subject Terms: |
Human induced pluripotent stem cells; Perfused blood vessels; Diabetic cells |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Science Advances; Gil CH, Chakraborty D, Vieira CP, et al. Specific mesoderm subset derived from human pluripotent stem cells ameliorates microvascular pathology in type 2 diabetic mice. Sci Adv. 2022;8(9):eabm5559. doi:10.1126/sciadv.abm5559; https://hdl.handle.net/1805/33097 |
| Availability: |
https://hdl.handle.net/1805/33097 |
| Rights: |
Attribution-NonCommercial 4.0 International ; http://creativecommons.org/licenses/by-nc/4.0/ |
| Accession Number: |
edsbas.9007155D |
| Database: |
BASE |