Effects of Mesenchymal Stem Cell and Growth Factor Delivery on Cartilage Repair in a Mini-Pig Model

Fisher, Matthew B. and Belkin, Nicole S. and Milby, Andrew H. and Henning, Elizabeth A. and Soeegaard, Nicole and Kim, Minwook and Pfeifer, Christian and Saxena, Vishal and Dodge, George R. and Burdick, Jason A. and Schaer, Thomas P. and Steinberg, David R. and Mauck, Robert L. (2016) Effects of Mesenchymal Stem Cell and Growth Factor Delivery on Cartilage Repair in a Mini-Pig Model. CARTILAGE, 7 (2). pp. 174-184. ISSN 1947-6035, 1947-6043

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Abstract

Objective We have recently shown that mesenchymal stem cells (MSCs) embedded in a hyaluronic acid (HA) hydrogel and exposed to chondrogenic factors (transforming growth factor-3 [TGF-3]) produce a cartilage-like tissue in vitro. The current objective was to determine if these same factors could be combined immediately prior to implantation to induce a superior healing response in vivo relative to the hydrogel alone. Design Trochlear chondral defects were created in Yucatan mini-pigs (6 months old). Treatment groups included an HA hydrogel alone and hydrogels containing allogeneic MSCs, TGF-3, or both. Six weeks after surgery, micro-computed tomography was used to quantitatively assess defect fill and subchondral bone remodeling. The quality of cartilage repair was assessed using the ICRS-II histological scoring system and immunohistochemistry for type II collagen. Results Treatment with TGF-3 led to a marked increase in positive staining for collagen type II within defects (P < 0.05), while delivery of MSCs did not (P > 0.05). Neither condition had an impact on other histological semiquantitative scores (P > 0.05), and inclusion of MSCs led to significantly less defect fill (P < 0.05). For all measurements, no synergistic interaction was found between TGF-3 and MSC treatment when they were delivered together (P > 0.05). Conclusions At this early healing time point, treatment with TGF-3 promoted the formation of collagen type II within the defect, while allogeneic MSCs had little benefit. Combination of TGF-3 and MSCs at the time of surgery did not produce a synergistic effect. An in vitro precultured construct made of these components may be required to enhance in vivo repair in this model system.

Item Type: Article
Uncontrolled Keywords: HYALURONIC-ACID HYDROGELS; AUTOLOGOUS CHONDROCYTE IMPLANTATION; ENGINEERED CARTILAGE; IN-VIVO; OSTEOCHONDRAL DEFECTS; ARTICULAR-CARTILAGE; CHONDROGENIC DIFFERENTIATION; ALGINATE MICROSPHERES; STROMAL CELLS; MATRIX; cartilage; repair; mesenchymal stem cells; TGF-3; animal models
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Unfallchirurgie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 25 Mar 2019 07:51
Last Modified: 25 Mar 2019 07:51
URI: https://pred.uni-regensburg.de/id/eprint/3180

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