RFA-DK-26-306: Engineering Improved Stem Cell-Derived Islet Cells for Replacement Therapies

Research Focus

This funding opportunity targets the engineering of stem cell-derived islet cells (SC-islets) to improve transplantation outcomes for type 1 diabetes (T1D). While clinical islet transplantation can restore glucose regulation, cadaveric donor scarcity and chronic immunosuppression burden have limited its application. SC-islets generated from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) offer a scalable alternative, but current products have limitations in durability, functional competence, and graft viability. This RFA seeks preclinical research on bioengineering approaches—including immune evasion strategies, safety switches, cell composition optimization, vascularization/innervation enhancement, and stress resilience—to create more robust SC-islet products. Research should leverage advances in islet biology (alpha/delta cell function, sex-specific responses, insulin genetics) and employ detailed post-transplant characterization of cell identity, glucose dynamics, and protein expression validation in relevant preclinical models.

At a Glance

• Who can apply: U.S. higher education institutions, nonprofits, for-profit organizations, government agencies, and tribal governments. Foreign organizations and foreign subawards/subcontracts are not eligible.
• Funding & project length: $3 million total (FY 2026) for 4–6 awards; $500,000 direct costs/year maximum; 5-year project period maximum.
• Award mechanism: R01 Research Project Grant (new applications only).
• Key dates: Applications open February 6, 2026; earliest start July 2026; scientific merit review October 2026; advisory council review December 2026.
• Best fit for: Stem cell biologists, immunologists, and T1D researchers developing cell engineering strategies (gene editing, protein expression, manufacturing optimization) to enhance SC-islet transplant efficacy without clinical trials.

Out of Scope

Applications proposing transplant site engineering, encapsulation devices, co-transplantation scaffolds, accessory cell engineering, or xenogeneic insulin-producing cells will be administratively withdrawn.