# Mesenchymal stem cell therapy for endothelial dysfunction in diabetes

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $538,561

## Abstract

Project Summary
This program will have a major impact in the field of cell-based therapy for the leading cause of death and
disability in patients with type 2 diabetes (DM), namely cardiovascular disease (CVD). Endothelial dysfunction
underlies the high rates of CVD associated with long-term DM. We will conduct a phase I/II, randomized
double-blind study testing the efficacy and safety of allogeneic bone marrow derived mesenchymal stem cells
(MSCs) vs. placebo in patients with type 2 DM, endothelial dysfunction and ischemic heart disease. This trial is
built on a solid foundation of 6 phase I/II trials conducted by our group that evaluated the safety and efficacy of
autologous and allogeneic MSCs in patients with ischemic and non-ischemic CVD. MSCs improve endothelial
progenitor cell (EPC) function and systemic endothelial function (measured by brachial artery flow-mediated
dilation, FMD%) in patients with ischemic as well as non-ischemic cardiomyopathy, including non-DM and DM
patients, suggesting that we now have a means to target a primary cause of the CV manifestations of DM.
Moreover, the effect on EPCs and FMD% was sustained (3 months after MSC administration) and evident in
patients receiving allogeneic, but not autologous, MSCs. Accordingly, this phase I/II study is timely, warranted,
and could have a major health impact by addressing an unmet need in a large population of patients at risk for
myocardial infarction, heart failure, sudden cardiac death, and recurrent hospitalizations. This study will break
new ground in the field in several respects. It will establish the efficacy of allogeneic MSC intravenous (IV)
delivery on systemic endothelial function (assessed by EPC function and FMD%) as well as coronary artery
endothelialization and vessel healing post-percutaneous coronary intervention (PCI). Although safety has
already been established by previous phase I/II trials of intravenous MSC delivery, additional safety data will
be determined from this DM population with ischemic heart disease. The proposed study will accomplish 3
aims: 1) Test the hypothesis that IV delivery of allogeneic MSCs stimulates EPC function and circulating
angiogenic growth factors and improves FMD% in type 2 DM patients; 2) Test the hypothesis that IV delivery of
MSCs improves 3 month post-PCI endothelialization and vessel healing in DM patients (assessed using optical
coherence tomography); 3) Test the hypothesis that allogeneic MSCs promote endothelial repair through
rescue of bone marrow progenitors in DM patients with ischemic heart disease. Bone marrow biopsies will be
obtained from DM patients at 3 months after MSC or placebo infusion for a detailed molecular and functional
assessment of the effect of IV allogeneic MSCs on bone marrow autologous MSC and EPCs. Together, the
studies proposed in this application will advance our understanding of this promising cellular-based therapy
and address a major unmet need in DM patients with CVD. This clinical tria...

## Key facts

- **NIH application ID:** 9968336
- **Project number:** 5R01HL134558-05
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Joshua M Hare
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $538,561
- **Award type:** 5
- **Project period:** 2016-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968336

## Citation

> US National Institutes of Health, RePORTER application 9968336, Mesenchymal stem cell therapy for endothelial dysfunction in diabetes (5R01HL134558-05). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9968336. Licensed CC0.

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