# Vascularized NICHE with local immunosuppression for cell replacement for Type 1 diabetes

> **NIH NIH R01** · METHODIST HOSPITAL RESEARCH INSTITUTE · 2022 · $798,092

## Abstract

Cell encapsulation technologies are poised to improve conventional islet transplantation to more effectively
manage type I diabetes. Currently, lifelong whole-body immunosuppression is administered to avoid immune
rejection of the transplant, despite the associated life-threatening adverse effects. Clinical studies reveal that
transplants eventually fail due to lack of vascular support for nutrients and oxygen supply and host immune
rejection. To address all these critical needs and supported by preliminary studies, we propose the NICHE, an
innovative subcutaneous vascularized encapsulation system with local elution of immunosuppressants to protect
transplanted cells from immune rejection. The NICHE presents dual transcutaneously refillable reservoirs, for
drug and cells, respectively, separated by a nanoporous membrane. Local immunosuppressant delivery confines
drugs to the graft site where immune attack occurs, minimizing exposure to the rest of the body, thus avoiding
systemic immunosuppression and associated adverse effects. The NICHE cell reservoir is fully vascularized with
functional vessels, recreating an ideal physiological environment conducive for maintaining long-term viability
and function of transplanted cells. We hypothesize that the NICHE will provide a vascularized environment
with local immunosuppressant delivery conducive for successful long-term islet allotransplantation to
restore euglycemia in diabetic nonhuman primates (NHP). In aim 1, we will study the efficacy and safety of
local immunosuppressant combinations as well as characterize their release from the NICHE via in vitro studies.
This will be followed in aim to define the optimal local immunosuppression regimen for islet allotransplantation
in NICHE and establish drug pharmacokinetics (PK) and biodistribution in healthy NHP. In aim 3, we will evaluate
the curative efficacy of NICHE with allotransplanted islets to restore and maintain euglycemia in diabetic NHPs
for one year. The proposed studies are based on our team’s extensive expertise in implantable drug and cell
delivery systems, tissue engineering, research and clinical transplantation, transplant immunology, type 1
diabetes, as well as supportive preliminary data and previously published work. Importantly, the NICHE is
designed prioritizing clinical considerations of efficacy, safety and user acceptability. Transcutaneous cell and
drug refilling allow for ease of drug replenishment when needed, thus extending implant lifespan potentially for
the lifetime of patients. Further, the thin and compact size of the NICHE, which is smaller than the encapsulation
implants under clinical investigation, is favorable for user acceptability. Successful completion of the proposed
work will provide a broadly applicable encapsulation system with localized immunosuppressant delivery for long-
term protection of transplanted islets, as well as minimize adverse effects associated with immunosuppressive
drugs. This could translate...

## Key facts

- **NIH application ID:** 10511952
- **Project number:** 1R01DK133610-01
- **Recipient organization:** METHODIST HOSPITAL RESEARCH INSTITUTE
- **Principal Investigator:** Alessandro Grattoni
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $798,092
- **Award type:** 1
- **Project period:** 2022-09-12 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10511952

## Citation

> US National Institutes of Health, RePORTER application 10511952, Vascularized NICHE with local immunosuppression for cell replacement for Type 1 diabetes (1R01DK133610-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10511952. Licensed CC0.

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