| First Author | Yoshihara E | Year | 2020 |
| Journal | Nature | Volume | 586 |
| Issue | 7830 | Pages | 606-611 |
| PubMed ID | 32814902 | Mgi Jnum | J:297404 |
| Mgi Id | MGI:6472584 | Doi | 10.1038/s41586-020-2631-z |
| Citation | Yoshihara E, et al. (2020) Immune-evasive human islet-like organoids ameliorate diabetes. Nature 586(7830):606-611 |
| abstractText | Islets derived from stem cells hold promise as a therapy for insulin-dependent diabetes, but there remain challenges towards achieving this goal(1-6). Here we generate human islet-like organoids (HILOs) from induced pluripotent stem cells and show that non-canonical WNT4 signalling drives the metabolic maturation necessary for robust ex vivo glucose-stimulated insulin secretion. These functionally mature HILOs contain endocrine-like cell types that, upon transplantation, rapidly re-establish glucose homeostasis in diabetic NOD/SCID mice. Overexpression of the immune checkpoint protein programmed death-ligand 1 (PD-L1) protected HILO xenografts such that they were able to restore glucose homeostasis in immune-competent diabetic mice for 50 days. Furthermore, ex vivo stimulation with interferon-gamma induced endogenous PD-L1 expression and restricted T cell activation and graft rejection. The generation of glucose-responsive islet-like organoids that are able to avoid immune detection provides a promising alternative to cadaveric and device-dependent therapies in the treatment of diabetes. |
