# Monitoring graft responses to the transplant niche in allogeneic cell replacement therapy

> **NIH NIH R44** · MINUTIA, INC. · 2024 · $870,000

## Abstract

Project Summary/Abstract
Patients living with Type 1 Diabetes regulate their blood glucose through daily exogenous insulin
administration – the only other option towards a path to insulin independence is donor islets/whole organ
transplant, a limited resource, that replaces the cohort of cells that are lost in patients due to an autoimmune
attack. The success of these transplants is highly variable, with several patients requiring a second or
sometimes a third infusion of donor cells. Failure of allogeneic cell/tissue transplant often results from immune
activation within the host, and strong systemic immunosuppression is necessary for successful engraftment of
the transplant. Numerous approaches have been undertaken to alleviate the need for systemic
immunosuppression – those focused on manipulating the graft have genetically removed the expression of cell
surface proteins that, when mis-matched, lead to activation of the adaptive and innate immune systems. Such
cells are potentially invisible to the immune system and pose the grave problem of serving as potential
reservoirs of infection. If we had a method of identifying when a graft was experiencing inflammatory stress, we
could design acute anti-inflammatory therapies to protect the graft from the assault – prolonging the time it
takes for the graft to get accustomed to the niche and begin functioning. More recently, stem cells have
emerged as a limitless resource of cells as a surrogate to donor islets, and early clinical attempts are currently
underway. Replacement with stem cell derivatives circumvents the roadblock of limited transplant material –
they are still faced with immune activation due to an allo-response after transplantation.
Our goal is to address these challenges using state-of-the-art technologies we have pioneered. Combining the
potential of stem cell therapy with an intracellular biosensing system that provides real time feedback in
response to the transplantation niche, we will leapfrog allogeneic cell transplantation into the future – such a
detection system can measure viability of grafts that can be predictive of successful engraftment and help
define interventions to protect cells against inflammatory stress soon after transplantation. We have
engineered nanoprobes that bind and respond to changes in miRNA levels and serve as intracellular sensors
for cell health. Our nanoprobes are specific, sensitive, and can be detected in vivo in animal models.
Here, we test our lead inflammation-sensitive biosensor in stem cell-derived insulin producing organoids – this
combination can provide unique spectral read outs, in vitro and in small animal models, that result from a
specific inflammatory response triggered in the cells, de-risking our final cell therapy product that will become
part of a functional cure for patients living with type 1 diabetes.

## Key facts

- **NIH application ID:** 10931682
- **Project number:** 5R44DK130034-03
- **Recipient organization:** MINUTIA, INC.
- **Principal Investigator:** Catherine Digovich
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $870,000
- **Award type:** 5
- **Project period:** 2021-09-06 → 2025-08-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10931682

## Citation

> US National Institutes of Health, RePORTER application 10931682, Monitoring graft responses to the transplant niche in allogeneic cell replacement therapy (5R44DK130034-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10931682. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*