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Korol, R.* ; Even-Ram, S.* ; Molakandov, K.* ; Puchinsky, D.* ; Hemed, M.* ; Mizrahi, N.* ; Toledo, I.* ; Lazar, D.* ; Chebath, J.* ; Tritel, M.* ; Ofir, R.* ; Ludwig, B. ; Revel, M.* ; Shapiro, A.M.J.* ; Bornstein, S.R.

Extracellular matrix-guided islet cell transplantation results in improved glycemic control in a NOD-SCID mouse model.

Horm. Metab. Res., DOI: 10.1055/a-2734-1983 (2025)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Current insulin therapy fails to fully restore physiological glucose homeostasis in type 1 diabetes mellitus, with 75% of patients unable to achieve the desired management targets. While stem cell-derived islets offer promising therapy, they require an enhanced extracellular matrix support for optimal transplantation outcomes. To address this challenge, we developed biofunctional endocrine micro-pancreata using decellularized porcine lung scaffolds seeded with embryonic stem cell-derived islets. In vivo efficacy was evaluated following subcutaneous or intraperitoneal transplantation into NOD-SCID mice, followed by streptozotocin induction of diabetes, with the comprehensive assessment of human insulin secretion, glucose homeostasis, and graft integration over 3 months. Our results demonstrated that endocrine micro-pancreata exhibited 1.4-fold-increased glucose-stimulated insulin secretion in vitro compared to non-responsive free islets. In vivo, endocrine micro-pancreas recipients maintained significantly lower glucose levels than controls throughout the experiment. Subcutaneous endocrine micro-pancreata showed superior performance, with 46% improved glucose tolerance versus 31% improvement for intraperitoneal delivery. Extensive CD31-positive neovascularization as well as insulin staining confirmed successful graft integration and sustained insulin production. Endocrine micro-pancreata provide a scalable platform for diabetes cell therapy, demonstrating sustained insulin secretion and improved glycemic control. The preserved extracellular matrix microenvironment supports islet function and vascularization, offering significant potential for clinical translation.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Diabetes ; Ecm ; Islets; Beta-cells; Streptozotocin
ISSN (print) / ISBN 0018-5043
e-ISSN 1439-4286
Journal Hormone and Metabolic Research
Publisher Thieme
Publishing Place Oswald-hesse-strasse 50, D-70469 Stuttgart, Germany
Reviewing status Peer reviewed
Institute(s) Institute of Pancreatic Islet Research (IPI)