PuSH - Publikationsserver des Helmholtz Zentrums München

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 möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Diabetes ; Ecm ; Islets; Beta-cells; Streptozotocin
ISSN (print) / ISBN 0018-5043
e-ISSN 1439-4286
Zeitschrift Hormone and Metabolic Research
Verlag Thieme
Verlagsort Oswald-hesse-strasse 50, D-70469 Stuttgart, Germany
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Pancreatic Islet Research (IPI)