# Autologous BM-MSCs and Islet Co-transplantation to Enhance Islet Survival and Function in TP-IAT Patients

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2021 · $632,231

## Abstract

Project Summary:
Total pancreatectomy and islet autotransplantation (TP-IAT) are currently performed in around 20 centers
worldwide for the treatment of chronic pancreatitis (CP). Major problems associated with TP-IAT are poor islet
engraftment and dysfunction after intraportal infusion. Because of these issues, only around 20% of the non-
diabetic CP patients are insulin-independent after surgery. Currently, interventional protocols to increase the
survival of the islet graft following transplantation are empiric. Thus, effective therapies that can facilitate islet
cell engraftment and promote survival after transplantation are urgently needed.
Multiple studies including our own demonstrate that islet co-transplantation with mesenchymal stem cells (MSCs)
enhances islet engraftment, decreases number of islets needed to achieve normoglycemia in rodent and
nonhuman primate islet transplantation models. MSCs exert such effects mainly via direct cell-cell contact and
their paracrine secretion of protective molecules including insulin growth factor-1 (IGF-1), hepatocyte growth
factor (HGF), transforming growth factor β (TGF- β) and others. We are the first group who performed a pilot
NIH-funded clinical trial evaluating the feasibility of autologous bone marrow-derived ex vivo-expanded MSCs
(BM-MSCS) and islet co-transplantation in CP patients. Although only three subjects received MSC and islet co-
transplantation due to the pilot nature of the grant, our data showed that BM-MSCs and islet co-transplantation
was a safe and promising strategy to improve islet engraftment after transplantation. Based on this unique clinical
trial experience and animal studies, the goal of this study is to further evaluate the safety and efficacy of
autologous MSCs and islet co-transplantation in a larger TP-IAT patient population. Our hypothesis is that co-
transplantation of islets with autologous BM-MSCs can enhance islet survival and function after transplantation,
resulting in more CP patients being diabetes free after TP-IAT. A critical part of this trial will be to define the
mechanisms by which MSCs modulate β cell survival and explore cellular and molecular biomarkers that can be
used as indicator(s) for β cell death and the potential response/efficacy of MSC therapy. Results from these
studies are not only urgently needed for the prevention of post-surgical diabetes in CP patients, but also may
offer useful information on which to address the more complex allogeneic islet cell transplantation for patients
with type 1 diabetes.

## Key facts

- **NIH application ID:** 10315988
- **Project number:** 1R01DK126454-01A1
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Hongjun Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $632,231
- **Award type:** 1
- **Project period:** 2021-08-24 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10315988

## Citation

> US National Institutes of Health, RePORTER application 10315988, Autologous BM-MSCs and Islet Co-transplantation to Enhance Islet Survival and Function in TP-IAT Patients (1R01DK126454-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10315988. Licensed CC0.

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