Sylakowski, Kyle James
(2022)
Therapeutic Strategies of Matricellular Proteins in Cutaneous Wound Healing: Countervailing Chronic Wounds and Excessive Scarring.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Cutaneous wound healing is an intricate orchestration of three overlapping phases of repair that encompass numerous cell types, signaling cascades, and microenvironment modifications to reach a successful resolution with minimal scarring. Disruption of any of these steps will create an abnormal healing response resulting in either chronic ulceration or excessive scarring. It has become evident that the extracellular matrix (ECM) and its associated components are key orchestrators during this process. A subclass of non-structural ECM proteins called matricellular proteins has taken to the forefront as possible targets for therapeutic strategies using ECM components due to their ability to mediate cell-ECM interactions. Here, we utilize two matricellular proteins significantly upregulated during the early or late phases of cutaneous wound healing – Tenascin-C (TNC) and Decorin (DCN). TNC is considered a vital on-switch for early phases of wound healing as it coordinates migration and survival signals of numerous cell types in the early stages of the hostile wound environment. Building upon previous work that showed TNC’s ability to promote survival of mesenchymal stem cells (MSCs) both in vitro and in vivo, we show that TNC enhances the therapeutic efficacy of MSCs through an improved ability to promote angiogenesis. DCN is the opposite of TNC as it is considered an essential off-switch for the tissue replacement phase of wound healing and limiting the occurrence of excessive scarring pathologies. Here we show DCN’s ability to improve wound healing outcomes and limit hypertrophic scarring in vivo during the resolution phase of repair. Ultimately, our work further emphasizes the potential use of matricellular proteins as therapeutic strategies to enhance cutaneous wound healing outcomes.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
2 May 2022 |
| Date Type: |
Publication |
| Defense Date: |
2 February 2022 |
| Approval Date: |
2 May 2022 |
| Submission Date: |
19 April 2022 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
150 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Cellular and Molecular Pathology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Mesenchymal Stem Cells, Dynamic Reciprocity, Cell Therapy, Autophagy, Ischemia |
| Date Deposited: |
02 May 2022 20:37 |
| Last Modified: |
02 May 2022 20:37 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/42667 |
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