# Project 2: Gender Dimorphism in Bone Marrow Endothelial Progenitor Cell-mediated Post-Infarct Myocardial Repair

> **NIH NIH P01** · TEMPLE UNIV OF THE COMMONWEALTH · 2021 · $435,875

## Abstract

Summary
Cardiovascular disease (CVD) is a leading cause of mortality across the world in both men and women,
however, abundant data from the literature underscore a significant disparity between men and women for
the incidence and severity of CVD. It has been observed that men undergo more rapid progression of heart
failure, less preservation of myocardial mass as they age, and worse age-matched cardiac contractility
compared to women. Moreover, women are exposed to a lower ischemic heart complication than age-
matched men both in the reproductive and postmenopausal age. These protection remain present even in
neonatal, prepubescent and postmenopausal populations where there is greater homogeny of hormones
between males and females indicating that although gonadal hormones do have an impact on differing
incidences of disease processes among men and women, there is more to the equation. The underlying
mechanisms responsible for this gender disparity beyond recognized effects of female sex hormones remain
understudied. Stem cell-based therapies, particularly those employing bone marrow progenitors, have
emerged as a potential novel therapeutic approach in ischemic tissue repair however patient population for
available clinical trials remain disproportionately biased towards inclusion of male patients (approximately
80% male subjects). Whether gender influences EPC/stem cell reparative properties has not been well
studied. Recently however, evidence has begun to emerge that gender does influence the functionality of
stem/progenitor cells, although mechanisms for such functional disparity are poorly understood. Our
preliminary studies indicate that bone marrow endothelial progenitor cells (EPCs) from female mice are more
efficient than those from male mice in the repair and angiogenesis in ischemic heart. Additionally, our data
indicates that molecular basis of this functional dimorphisms partly depends upon different epigenetic
landscape in cells from different genders which appears to be independent of sex hormones including
estrogen. Therefore our central hypothesis is that female derived BM- EPCs possess superior reparative
properties than their male counterparts and that functional superiority of female EPCs involves both
estrogen-dependent and estrogen-independent signaling and molecular mechanisms including a differential
epigenetic landscape. This project aims to study, in detail, phenotypic, epigenetic and molecular basis of
gender-specific differences in EPC reparative properties. This overall aim will be achieved by conducting
experiments organized under the following three specific aims: 1) To determine the role of gender dimorphism
on EPC -mediated post-MI repair; 2) To elucidate epigenetic mechanisms of functional disparity between
male and female EPCs; and 3) To test the therapeutic efficacy of gender specific-EPC- derived exosomes as
cell-free modality for post-MI repair.

## Key facts

- **NIH application ID:** 10145771
- **Project number:** 5P01HL147841-02
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Raj Kishore
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $435,875
- **Award type:** 5
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145771

## Citation

> US National Institutes of Health, RePORTER application 10145771, Project 2: Gender Dimorphism in Bone Marrow Endothelial Progenitor Cell-mediated Post-Infarct Myocardial Repair (5P01HL147841-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10145771. Licensed CC0.

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