Thursday, October 2, 2025 10/2/2025

Engineering Mesenchymal Stromal Cells to treat Muscle Fibrosis

Award Number: R00AR079561
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Engineering Mesenchymal Stromal Cells to treat Muscle Fibrosis - Project Summary Mesenchymal stromal cells (MSCs) have been tested in nearly one thousand clinical trials, mostly because of their ability to secrete factors that can modify host environments. For instance, MSCs can adapt to their niches and remodel the extracellular matrix. While this property of MSCs can potentially be beneficial to treat fibrosis and promote tissue regeneration, leveraging this property has been challenging because specific signals that enable MSCs to remodel the matrix remain to be defined and leveraged in MSC-based therapeutics. Here, we describe a highly efficient approach to encapsulate individual cells in engineered gel coatings with specifically defined biophysical and biochemical cues. We have developed this approach to show that soft, thin gel coating is an enabling cue that increases the production of soluble interstitial collagenases in response to tumor necrosis factor-α (TNFα). Importantly, our preliminary data show that gel-coated MSCs decrease collagen deposition in a murine muscular dystrophy model. In this K99/R00 proposal, I will build upon these results to test the hypothesis that programming of MSCs using specifically engineered microgels activates the potential of MSCs to inhibit muscle fibrosis. In Aim 1, we will determine the role of engineered gel coating in TNFα- induced activation of MSCs to produce high levels of interstitial collagenases and degrade collagen, and understand mechanisms behind this process. In Aim 2, we will investigate the role of gel-coated MSCs in inhibiting muscle fibrosis and restoring muscle functions. Success of this proposal will lead to an effective strategy to treat muscle fibrosis, which is a major unmet clinical need. During the K99 phase, I will work with my advisory committee to enhance my knowledge in biomaterial design, cellular mechanobiology, pathophysiology of fibrosis, as well as advanced microtechnologies, imaging, and computational approaches to effectively drive this research project. These experiences together with career development activities described in this proposal will ensure my smooth transition to an independent investigator at the interface between mechanobiology and bioengineering to develop novel therapeutic strategies for muscle disorders.


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: 2025 ( Subtotal = $231,257 )
2025	2025	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	5/6/2025	NON-COMPETING CONTINUATION	$231,257
														Subtotal = $231,257

Issue Date FY: 2024 ( Subtotal = $315,969 )
2024	2024	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	4	5/20/2024	NON-COMPETING CONTINUATION	$236,501
2024	2023	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	11/16/2023	EXTENSION WITH OR WITHOUT FUNDS	$79,468
														Subtotal = $315,969

Issue Date FY: 2023 ( Subtotal = $249,001 )
2023	2023	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	8/31/2023	EXTENSION WITH OR WITHOUT FUNDS	$249,001
														Subtotal = $249,001

Grand Total All Awards = $796,227

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Engineering Mesenchymal Stromal Cells to treat Muscle Fibrosis

Award Number: R00AR079561

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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