# Novel Gene and Stem Cell Therapy for Type 1 Diabetes

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $529,169

## Abstract

Project Summary:
An optimal intervention of type 1 diabetes (T1D) should effectively targets the immune system, protects
pancreatic β cells from death, and regenerates β cells. Currently there are no single intervention can achieve
these effects. Novel combined therapies that can take advantages of each single therapy would be beneficial for
a complex disease as T1D. The use of mesenchymal stromal/stem cells (MSCs) as a therapeutic tool represents
a promising new intervention as increasing evidence demonstrates that MSC therapy can effectively target
several injury pathways in a variety of autoimmune and inflammatory diseases, something that most
pharmacological interventions cannot accomplish. Following tissue injuries, MSCs exert protective effects
through the release of pro-mitotic, anti-apoptotic, anti-inflammatory, and immunomodulatory soluble factors, while
mitigating metabolomic and oxidative stress imbalance and restoring homeostasis. MSC infusion reversed
diabetes in rodent models and prevents decrease of c-peptide in patients with new onset T1D. In our NIH-funded
clinical trial, co-transplantation of autologous MSCs with islets improved glycemic control after transplantation in
chronic pancreatitis patients. Our recent studies shown that MSC infusion promote T regulatory cell generation
and protect islets from death. However, most human studies using MSC alone have not been successful at
sustained suppression of the autoimmune response. Based on the ability of alpha-1 antitrypsin (AAT) to
decrease B-cell activating factor, decrease anti-insulin auto-antibodies, promote tolerogeneic dendritic cells and
promote Treg function, we propose to combine AAT and MSCs to demonstrate sustained efficacy in humanized
mouse models of TID. Based on these studies, the goal of this proposal is to determine whether AAT engineered
human MSCs that can target the autoimmune response in T1D in a more sustained way in humanized mouse
models. Our central hypothesis is that bile duct infusion of AAT overexpressing MSCs effectively prevents and/or
reverses autoimmune diabetes by protecting Tregs from apoptosis and dysfunction and by improving β cell
survival and/or regeneration. We will test this hypothesis by determining the protective effects of MSCs or AAT-
MSCs infusion on β cells and whether AAT-engineered MSCs are more potent for the treatment of diabetes
when these cells are co-transplanted with human islets into streptozotocin-induced diabetic humanized
NOD/SCID/IL-2γ-/- (Hu-NSG) or the NOD mice.

## Key facts

- **NIH application ID:** 9972887
- **Project number:** 5R01DK120394-03
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Hongjun Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $529,169
- **Award type:** 5
- **Project period:** 2018-09-30 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972887

## Citation

> US National Institutes of Health, RePORTER application 9972887, Novel Gene and Stem Cell Therapy for Type 1 Diabetes (5R01DK120394-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9972887. Licensed CC0.

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