Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Intravenously injected mesenchymal stromal cells protect against Acute Lung Injury by transferring mitochondria to restore endothelial function

Award Number: R01HL175058
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2025
PERIOD OF PERFORMANCE END DATE: 06/30/2029

Group Awards By:

View Award Description

Intravenously injected mesenchymal stromal cells protect against Acute Lung Injury by transferring mitochondria to restore endothelial function - PROJECT SUMMARY Significance. Acute lung injury (ALI) is a major cause of mortality and morbidity, but a cure is still not available. Recent preclinical studies show the potential for ALI therapy with bone marrow-derived mesenchymal stromal cells (BMSCs). However, the BMSC protective mechanisms are incompletely understood. Our goal is to define mechanisms regulating BMSC interactions with endothelial cells in situ to define mitochondrial mechanisms responsible for protection against ALI. Hypothesis. We propose the novel hypothesis that, in ALI, intravascularly (i.v.) administered BMSCs are retained by selectin and Cx43-induced mechanisms leading to mitochondrial transfer to endothelial cells in situ. We also propose that BMSCs protect against ALI by restoring mitochondrial function, resulting in the reinstatement of the mitochondrial calcium uniporter (MCU) in endothelial mitochondria, re-establishing mitochondrial Ca2+ buffering, and strengthening the endothelial barrier. Specific Aims. The specific aims are to evaluate molecular mechanisms of BMSC attachment to lung endothelium in situ (Aim 1), and to determine the barrier-protective effects of BMSC to endothelial mitochondrial transfer (Aim 2). Approach. We will achieve these aims by live confocal microscopy of mouse lungs, and precision cut slices of mouse and human lungs. Our determinations will include (1) evaluation of selectins and connexin 43 in BMSC attachment; (2) evaluation of mitochondrial transfer as the regulator of endothelial Ca2+ buffering by Ca2+ transit across the MCU; (3) quantifications of endothelial Ca2+, and live f-actin as barrier determinants; (4) strategies for engineering BMSC mitochondria to enhance their efficacy after transfer. Preliminary data. We show (1) BMSCs interact with and transfer mitochondria to endothelial cells in situ; (2) ALI downregulates lung MCU and, thus, blocks Ca2+ buffering, causing endothelial Ca2+ increase and endothelial barrier weakening; (3) Intravenously administered BMSCs rescue MCU, strengthen the barrier and ameliorate ALI. These and other preliminary data on our measurement strategies support the feasibility of the proposal. Impact. This proposal will provide the first systematic interrogation of interactions between i.v. administered BMSCs and endothelial cells of intact lung microvessels, as well as lung protective mechanisms subsequent to BMSC mitochondrial transfer to the endothelium. Mechanisms relating the transfer to endothelial barrier enhancement will be realized for the first time. Strategies for enhancing the efficacy of BMSC mitochondria will be developed. The translational relevance of the hypothesis will be evaluated in human lung slices.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2025	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BLVD	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	001	2	6/3/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$670,551
2026	2025	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Lung Diseases Research	000	1	5/22/2026	NEW	-$670,551
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $761,262 )
2025	2025	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Lung Diseases Research	000	1	8/17/2025	NEW	$761,262
														Subtotal = $761,262

Grand Total All Awards = $761,262

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Intravenously injected mesenchymal stromal cells protect against Acute Lung Injury by transferring mitochondria to restore endothelial function

Award Number: R01HL175058

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2025

PERIOD OF PERFORMANCE END DATE: 06/30/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer