Localized immunomodulation with cytokine-producing cells to mitigate foreign body responses in rodents and a nonhuman primate.

Authors

Boram Kim, Dilrasbonu Vohidova, Amanda Nash, Yuen San Chan, Samantha Fleury, Shravani Deo, Danna Murungi, Peter D Rios, Ira Joshi, Hafsa Nasir, Daisy Lopez, Mor Sela Golan, Cassidy Hart, Jose Oberholzer, H Courtney Hodges, Omid Veiseh

Published in

Science advances. Volume 12. Issue 32. Pages eaec7053. Aug 07, 2026. Epub Aug 05, 2026.

Abstract

The efficacy of cell-based therapeutics is often compromised by host immune recognition of implanted cells and biomaterials, resulting in fibrotic encapsulation and loss of function. Here, we address this challenge with an immunomodulatory cell-based therapy, in which alginate-encapsulated retinal pigment epithelial cells continuously secrete cytokines to locally modulate the implant microenvironment. In a healthy rodent model, the localized production of interleukin-10 (IL-10) or IL-12 from encapsulated cytokine-producing cells prevented foreign body response to alginate capsules. Mechanistically, treatment was associated with reduced expression of profibrotic genes and immune shifts consistent with macrophage and T cell regulation, supporting a cytokine-mediated mitigation of foreign body response. In a diabetic murine model (streptozotocin-induced C57BL/6J), coimplantation of human islets with IL-10-producing cells attenuated pericapsular fibrosis, preserved islet viability, and restored normoglycemia for up to 100 days (4.76 times longer than islets alone). Notably, IL-10-producing cells were also effective in enabling the durability and function of encapsulated cells in a healthy nonhuman primate, showing translational feasibility. Collectively, these findings suggest that localized cytokine delivery can reduce fibrotic encapsulation and support durable graft function, offering a path to lessen reliance on systemic immunosuppression in islets transplantation and other implantable biomaterial therapies.

PMID:
42555743
Bibliographic data and abstract were imported from PubMed on 06 Aug 2026.

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