# A novel approach for treating diabetes using pulsed focused ultrasound and intra-arterial delivery of mesenchymal stem cell based therapies directly into the pancreas

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $455,039

## Abstract

PROJECT SUMMARY
Treatment for type 1 diabetes (T1D) involves life-long daily injections of insulin to ensure tight metabolic control.
However, recent studies have shown that diabetic patients still have residual functional β cells within their
pancreas and hence therapeutic interventions that could recover and/or regenerate β cell quantity and function
would have a profound impact on these patients. A promising approach to preserve and regenerate β cells is to
deliver mesenchymal stem cell (MSC)-based therapies directly to the pancreas. MSCs can release
immunomodulatory, angiogenic, anti-inflammatory, anti-apoptotic and anti-fibrotic factors into their surrounding
microenvironment to modulate the immune system as well as stimulate the regeneration of damaged tissues;
these paracrine factors are released either in a soluble form or within extracellular vesicles (EVs). Studies have
shown that both parent MSCs (i.e. a cellular therapy) and MSC-derived EVs (i.e. a cell free therapy) can
improve the survival and function of islets. Unfortunately, the clinical translation of MSC-based therapies for the
treatment of diabetes has been sub-optimal, predominantly due to majority of MSCs and EVs getting trapped in
the lung and reticuloendothelial system, respectively, following conventional intravenous (IV) injection. Hence,
in the present proposal, we will: (i) investigate a novel approach using pulsed focused ultrasound (pFUS) to
gently shake and “prime” the pancreas to release chemicals which can attract and retain MSC-based therapies
that are delivered directly into the gland by intra-arterial (IA) injection and (ii) determine which source and
type of MSC-based therapy is best suited to regenerate and protect the diabetic pancreas. In Aim 1, we will
investigate the biological effects of pFUS, which is a clinically available technology, on the pancreatic gland,
individual pancreatic islets and different sources of MSCs. In pilot studies, we have found that soundwaves can
not only stimulate pancreatic islets and MSCs, but they can also induce the expression of chemoattractants (i.e.
cytokines, trophic factors, and cell adhesion molecules) in the pancreas; the latter will help to facilitate the
homing, permeation and retention of MSC-based therapies to struggling islets within the diabetic pancreas. In
Aims 2 (parent MSCs) and 3 (MSC-derived EVs), we will evaluate the effect of MSC-based therapies derived
from different sources (i.e. bone marrow, adipose tissue and umbilical cord) on regenerating the diabetic
pancreas when they are given directly into the gland via IA injection, before and after “priming” the pancreas with
pFUS. To achieve these aims, we developed a technique to deliver therapeutics directly into the pancreas, via
its arterial blood supply, which is designed to simulate what Interventional Radiologists can do using
endovascular techniques. In addition, we will use a novel device called ExoTIC to isolate MSC-derived EVs with
high purity and...

## Key facts

- **NIH application ID:** 10001496
- **Project number:** 5R01DK119293-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Avnesh Sinh Thakor
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $455,039
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001496

## Citation

> US National Institutes of Health, RePORTER application 10001496, A novel approach for treating diabetes using pulsed focused ultrasound and intra-arterial delivery of mesenchymal stem cell based therapies directly into the pancreas (5R01DK119293-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10001496. Licensed CC0.

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