# Mesenchymal Vascular Progenitor Depletion Promotes Lung Aging and Susceptibility to Emphysema

> **NIH NIH R35** · NATIONAL JEWISH HEALTH · 2022 · $996,000

## Abstract

The overall mission of this research program is to define how pulmonary Mesenchymal Vascular
Progenitor Depletion Promotes Lung Aging and Susceptibility to Emphysema. Loss of epithelial progenitor cell
function is a unifying factor in accelerated lung aging, and the development of emphysema. However, equally as
important but poorly understood, there is a gap in our understanding of mesenchymal vascular progenitors
(MVPC) in these processes. This proposal is significant as it attempts to fill in a number of important gaps
surrounding how dysfunction of the MVPC progenitor population, contributes to aging and increased
susceptibility to emphysema via regulation of vascular remodeling and loss of angiostasis. Analysis of the MVPC
- lung niche interactions provide a target rich environment to identify nuances in MVPC progenitor dependent
pathways relevant to the pathobiology of Angiostasis, Aging and Emphysema, as well as the potential to identify
therapeutics to restore tissue function. We propose three focus areas for our research based on complementary
themes. Theme 1 Regulation of MVPC function in healthy and aged lung: we will use our unique in vivo and in
vitro model systems to identify how MVPC function and adaptive angiogenesis is regulated during tissue
homeostasis and aging. Theme 2 Consequence of MVPC Loss of Function in healthy, aged and cigarette smoke
exposed lung: we will show that loss of MVPC function, by depletion or altered signaling, drives vasculopathy
and subsequent lung aging and emphysema. Theme 3 Therapeutic Rescue of MVPC function in aged and
cigarette smoke exposed lung: we will validate the use of MVPC and repurposing of FDA approved paquinimod
to restore MVPC numbers and function, subsequent tissue function and establish time frames for intervention.
Positive results from these studies are readily translatable. We will leverage our strong collaborations, at National
Jewish, University of Colorado as well as internationally recognized collaborators provide a basic and
translational understanding of the mechanisms regulating MVPC function and differentiation at the single cell
level as well as how they regulate their niche and lung microenvironment. We will also define whether progenitor
rescue with MVPC cell therapy or interventional treatment will restore lung structure and function.

## Key facts

- **NIH application ID:** 10353622
- **Project number:** 1R35HL161238-01
- **Recipient organization:** NATIONAL JEWISH HEALTH
- **Principal Investigator:** SUSAN M MAJKA
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $996,000
- **Award type:** 1
- **Project period:** 2022-01-01 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10353622

## Citation

> US National Institutes of Health, RePORTER application 10353622, Mesenchymal Vascular Progenitor Depletion Promotes Lung Aging and Susceptibility to Emphysema (1R35HL161238-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10353622. Licensed CC0.

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