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The role of mechanical stimulation in macrophage-mediated skeletal muscle regeneration in an in vitro injury model

Award Number: F31AR075367
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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Project Summary/Abstract Severe muscle injuries resulting from trauma, strain, or contusion are very common yet still present a significant clinical challenge since there is no therapy currently available to restore full function to the damaged tissue. Instead, severe muscle injuries often heal via fibrosis, leading to contracture, pain, and disability. Since skeletal muscle is known to respond strongly to mechanical stimuli, recent studies have shown that the use of mechanical cues alone can effectively stimulate tissue regeneration. Investigation has provided evidence that the immune system, which plays a critical role in tissue repair, may be modulated by mechanical stimulation of the injured tissue. In this proposal, I will focus on investigating the role of mechanical signaling in immune cell-muscle interactions, specifically between macrophages and muscle progenitor cells (MPCs) since macrophages have been shown to play an important role in guiding MPC behavior during repair. I hypothesize that the regenerative effects of macrophages on injured skeletal muscle through their interactions with MPCs will be enhanced under specific conditions of applied cyclic tensile loading leading to improved recovery. I will develop an in vitro model of injured skeletal muscle containing myofibers and MPCs and introduce polarized macrophages into this system. I will design and fabricate a cyclic tensile loading device and use this system to explore the effects of cyclic tensile loading parameters, such as strain and frequency, on macrophage modulation of myofiber regeneration and functional repair of the injured skeletal muscle constructs. I will further evaluate potential mechanisms behind the observed results to understand how mechanical cues may be impacting the interaction between macrophages and MPCs. I hope that the proposed work can offer new insight into how mechanical stimulation can be used clinically as a method of promoting skeletal muscle repair. The knowledge that arises from these studies may enable the optimization of physical therapies to provide better outcomes in the clinical setting and may offer new therapeutic avenues for healing severe muscle injuries.


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: 2023 ( Subtotal = -$23,524 )
2023	2022	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	4	7/21/2023	NON-COMPETING CONTINUATION	-$3,022
2023	2022	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	4	11/28/2022	NON-COMPETING CONTINUATION	-$1
2023	2022	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	11/9/2022	NON-COMPETING CONTINUATION	-$20,501
														Subtotal = -$23,524

Issue Date FY: 2022 ( Subtotal = $30,752 )
2022	2022	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	5/13/2022	NON-COMPETING CONTINUATION	$30,753
2022	2022	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	4	8/26/2022	NON-COMPETING CONTINUATION	-$1
														Subtotal = $30,752

Issue Date FY: 2021 ( Subtotal = $32,947 )
2021	2021	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	4/16/2021	NON-COMPETING CONTINUATION	$32,947
														Subtotal = $32,947

Issue Date FY: 2020 ( Subtotal = $33,176 )
2020	2020	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	7/17/2020	NON-COMPETING CONTINUATION	$3,656
2020	2020	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	6/17/2020	NON-COMPETING CONTINUATION	$29,520
														Subtotal = $33,176

Issue Date FY: 2019 ( Subtotal = $35,054 )
2019	2019	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	3/15/2019	NEW	$0
2019	2019	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	3/15/2019	NEW	$35,054
														Subtotal = $35,054

Grand Total All Awards = $108,405

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The role of mechanical stimulation in macrophage-mediated skeletal muscle regeneration in an in vitro injury model

Award Number: F31AR075367

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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