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Effects of Circulating Factors and Progenitors on Wound Healing during Pregnancy

Award Number: R21AR073509
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Abstract: Wound healing is a complex biological process requiring growth factors and progenitor cells that act in concert to restore the integrity of the injured tissue. Fibrosis or scarring of tissue results from nonspecific repair as well as aberrant wound healing in response to tissue injury and not only predisposes tissue to a secondary injury but also contributes to 45–50% of deaths in the Western world. Increased age is a major risk factor for impaired wound healing due to tissue fibrosis. Many studies at the cellular and molecular level have examined age-related differences in wound healing and have identified an age-related decline in progenitor cells. It has been reported that exposure to factors present in the serum of young mice restores the regenerative capacity of aged progenitor cells. Also, fetal dermis has been shown to regenerate after injury without scarring, while adult skin wound healing usually results in scar tissue. Pregnancy represents a unique biological model of a naturally-shared circulatory system between young and old organisms. Our preliminary data have demonstrated improved muscle healing after injury in pregnant mice. More importantly, we have observed an improved myogenic differentiation capacity of aged muscle progenitor cells (MPCs) after stimulation with serum from pregnant mice, suggesting that circulating factors may influence the potency of stem cells in the mother during pregnancy. We hypothesize that circulating factors during pregnancy have beneficial effects on maternal wound healing, such as reduction in fibrosis for optimal tissue regeneration. Therefore, we propose, in Aim1, to determine whether pregnancy accelerates wound healing (skeletal muscle and skin) and which circulating factors in pregnancy are responsible for this beneficial effect. We will utilize previously described skin wound and muscle injury mouse models and adapt them to investigate the healing process, including fibrosis and contributing circulating factors, during pregnancy. In addition, we will obtain skin biopsies from pregnant and non-pregnant women after surgery to analyze tissue healing with respect to scarring at the biopsy site. It has been reported that fetal microchimeric cells (FMCs) can be found in the circulation and organs of mammals during pregnancy as a result of bidirectional passage of maternal and fetal cells. The presence of fetal cells in maternal circulation may play a beneficial role in repairing damaged maternal tissues. Little has been done to determine the exact roles of circulating fetal progenitor cells and how they interact with maternal progenitor cells during pregnancy with respect to wound healing. In Aim 2, we propose to determine which circulating fetal and maternal progenitor cells in pregnant mice are responsible for the beneficial effects on wound healing during pregnancy. Green fluorescent protein (GFP)- expressing male mice will be crossed with female mice without GFP, and GFP will be used to track FMCs. The Y chromosome will be used as an additional method to track the FMCs. Results from this study will identify rejuvenating factors and novel progenitor cells within blood circulation during pregnancy with potential for development of novel and clinically relevant therapies to improve wound healing and reduce fibrosis.


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: 2021 ( Subtotal = $0 )
2021	2019	STEADMAN PHILIPPON RESEARCH INSTITUTE	181 WEST MEADOW DRIVE	VAIL	CO	81657	EAGLE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	5/25/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $2,750 )
2020	2019	STEADMAN PHILIPPON RESEARCH INSTITUTE	181 WEST MEADOW DRIVE	VAIL	CO	81657	EAGLE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	11/12/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$2,750
														Subtotal = $2,750

Issue Date FY: 2019 ( Subtotal = $169,400 )
2019	2019	STEADMAN PHILIPPON RESEARCH INSTITUTE	181 WEST MEADOW DRIVE	VAIL	CO	81657	EAGLE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	7/16/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$169,400
2019	2019	STEADMAN PHILIPPON RESEARCH INSTITUTE	181 WEST MEADOW DRIVE	VAIL	CO	81657	EAGLE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	2	8/6/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$155,445
2019	2018	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	7/16/2019	NEW	$0
2019	2018	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	1	8/6/2019	NEW	-$155,445
														Subtotal = $169,400

Issue Date FY: 2018 ( Subtotal = $203,280 )
2018	2018	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	5/23/2018	NEW	$203,280
														Subtotal = $203,280

Grand Total All Awards = $375,430

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Effects of Circulating Factors and Progenitors on Wound Healing during Pregnancy

Award Number: R21AR073509

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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