Liou, Jr-Jiun
(2020)
Application of Platelet-Rich Plasma in Combination with Cell-Based Therapy for Cartilage Repair.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Post-traumatic and focal cartilage defects of the knee affect over three million Americans annually. Autologous cell-based therapy, e.g., autologous chondrocyte implantation, is limited by the need for ex vivo chondrocyte expansion and donor site morbidity. Mesenchymal stem cells (MSCs), owing to their relative ease of isolation, higher replication activity, and chondrogenic potential, represent an alternative reparative cell type. Platelet-rich plasma (PRP) is an autologous, growth factor-rich biologic that has recently received increasing attention and use as a therapeutic adjunct for the treatment of degenerative joint diseases, and there is evidence suggesting that PRP acts by promoting stem cell proliferation and tissue healing. In this research, we have examined the effects of PRP treatment on chondrogenic differentiation of adult human MSCs derived from the infrapatellar fat pad (IFP-ASCs), maintained in high-density pellet cultures and hydrogel-encapsulated cultures. Cells derived from the infrapatellar fat pad were shown to possess a greater chondrogenic potential than those derived from subcutaneous tissue, and ideally provide a convenient cell source for tissue regenerative procedures. Our results showed that IFP-ASC chondrogenesis is inhibited with increasing PRP concentrations and duration of exposure, based on histological, biochemical, and gene expression analyses. We identified vascular endothelial growth factor (VEGF) as a component of PRP that acts to impair the pro-chondrogenic activity of PRP on IFP-ASCs. We further tested the combination of ASCs with VEGF-depleted PRP encapsulated with hydrogels for in vivo osteochondral defect repair in a rabbit model. Findings from this research provide information on the potential application of PRP in combination with cell-based therapy for cartilage repair. Our goal is to develop an optimal cell and biologic formulation for a potential point-of-care treatment of post-traumatic and focal cartilage defects, for the restoration of joint function and improvement of the quality of life.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
29 January 2020 |
| Date Type: |
Publication |
| Defense Date: |
6 April 2018 |
| Approval Date: |
29 January 2020 |
| Submission Date: |
2 June 2018 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
118 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Swanson School of Engineering > Bioengineering |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
platelet-rich plasma, mesenchymal stem cells, chondrogenesis, cartilage repair |
| Date Deposited: |
29 Jan 2020 14:59 |
| Last Modified: |
29 Jan 2020 14:59 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/34569 |
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