nPOD. Beta Cell Physiology and Dysfunction

Evaluating senescence induction in human beta cells upon transplantation

We are interested in cell replacement therapy as a potential practical cure for patients suffering from diabetes. Using stem cell derived beta cell clusters and cadaveric human islets transplantation in preclinical animal models we find distinct changes to the beta cell phenotype. This project will test if our observations hold true in islet recipients. We will evaluate if the changes observed using model systems are also present in tissue sections from donors that previously received islet transplants.

We find a small subpopulation of stem cell derived beta cells (sBC) marked by CD9. We found previously that CD9 marks beta cell subpopulations that are less functional in cadaveric islets preps (Dorrell et al. Nature com, 2016). CD9 cell % is up in T2D. When looking closely, part of the CD9 population in both sBC and cadaveric islets exhibits a senescent and senescence associated secretory phenotype. When we look at transplanted sBC we see a huge increase in CD9 cells (and senescence markers). We are currently testing if CD9 cells exhibit greater immunogenicity. We believe our findings have important implications to current efforts aimed at providing a practical cure via cell replacement therapy to diabetes patients.

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