# Mechanisms for treating ischemic wounds with human adipocyte derived stem cell exosomes

> **NIH VA I01** · JAMES A. HALEY VA MEDICAL CENTER · 2022 · —

## Abstract

This research will develop an innovative therapy to promote tissue regeneration and reverse the
consequences of recalcitrant wound healing. It is particularly relevant to our Veteran population
that suffers the consequences of injury and aging. The $5 billion global market for “advanced
wound care” is anticipated to triple in the next ten years. We have a rapidly growing cohort of older
veterans with diabetes, a new cohort of wounded warriors with injuries that include non-healing
ulcers from spinal cord injury, multiple traumatic injuries and burns. Hence Veteran populations
are at risk for a staggering number of chronic wounds. We propose to use a secreted nanovesicle
from adipose derived stem cells (human ADSC). Adipose tissue is an abundant and renewable
source of stem cells. Human ADSC release trophic factors that stimulate endogenous repair
mechanisms in wounds, and they have immunomodulatory effects, responding to the
microenvironment. They have been shown to heal wounds. However, hADSC research is flawed
by the lack of standardization and delivery methods. Our goal is to harness the promise of stem
cell regenerative secreted factors to heal wounds. We have identified a wound healing treatment
using conditioned media (CM) collected from hADSC in culture. We recognize that CM contains
exosomes secreted by hADSC, and the factors within the exosomes act in a paracrine manner. In
addition to lipids and proteins, exosomes contain various species of RNA. One type, long non-
coding RNA, is of particular interest in that it is only secreted by stem cells. Once cells start to
differentiate to lineages such as bone and adipocytes, it is retained for a nuclear function. The
secreted long non-coding RNA that we find in exosomes is MALAT1. It functions in wound
healing, and we predict that exosomes rich in MALAT1 will be able to heal a variety of wounds.
We hypothesize that MALAT probably derepresses genes for migration, proliferation, and
angiogenesis via its interaction with microRNAs. We will examine how exosomes function in vitro in
a human dermal fibroblast wound healing assay. We will use a rat ischemic wound model for
examining how exosomes function in vivo. Both of these models will let us optimize the number
and concentrations of exosomes that allow for wound closure and modulation of angiogenesis. We
propose improvements to hADSC that will allow for collection of more exosomes. Exosomes are
more stable than stem cells for wound applications. They can be stored in low temperatures,
applied topically and be made available to wounds in emergency rooms and for home use. This
project is the first step in making hADSC exosomes a clinical reality for wound repair and tissue
regeneration.

## Key facts

- **NIH application ID:** 10489667
- **Project number:** 5I01BX003689-05
- **Recipient organization:** JAMES A. HALEY VA MEDICAL CENTER
- **Principal Investigator:** DENISE Ratzlaff COOPER
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10489667

## Citation

> US National Institutes of Health, RePORTER application 10489667, Mechanisms for treating ischemic wounds with human adipocyte derived stem cell exosomes (5I01BX003689-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10489667. Licensed CC0.

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