Characterizing T Cell Contribution to the Injury Microenvironment During Tissue Regeneration in African Spiny Mouse

Grants and Contracts Details

Description

It remains evident that most injuries caused by surgery, trauma or disease heal by fibrosis followed by the formation of scar tissue. Therapy to stimulate regeneration of musculoskeletal tissue in situ would alleviate much of the emotional and economic burden associated with our current imperfect therapies, but mammalian epimorphic regeneration continues to be an elusive target. While current work with stem cell transplantation, matrix and tissue engineering shows potential in several tissue types, there are significant challenges to overcome before achieving regeneration of musculoskeletal tissue. Mounting evidence demonstrates that the injury microenvironment is dynamic. How the molecular components change and affect resident cells to polarize the healing response is a key area of research. The long-term goal of our research is to understand the mechanistic basis for mammalian musculoskeletal regeneration in order to catalyze therapies that inhibit fibrosis and stimulate regeneration where it does not naturally occur. The objectives of this proposal are to characterize T cell phenotypes associated with regenerating and scarring microenvironments and to test how these cells drive local fibroblast behavior. Our central hypothesis is that a specific population of T cells, regulatory T (TREG) cells, are required for regeneration. TREG cells represent fundamental dominant-negative immune cells that coordinate inflammation. Despite the importance of TREG cells during the inflammatory response, how they contribute to regeneration in mammals remains unknown. In Aim 1, we will identify unique T cells subtypes associated with regeneration and scarring using scRNA-seq. Additionally, we will ablate TREG cells in spiny mice to test if they are necessary for regeneration. In Aim 2, we will investigate how T cells isolated from regenerating tissue direct dermal fibroblast behavior. The results of the proposed research will advance regenerative medicine by determining if T cell present in the injury microenvironment stimulate regeneration of musculoskeletal tissue.
StatusFinished
Effective start/end date9/1/198/31/22

Funding

  • National Institute of Dental and Craniofacial Research: $420,750.00

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