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Abstract Number: 850

Long Term Efficacy of Cartilage Repair Induced By scSOX9 in Situ with Bone Marrow-Derived Mesenchymal Stem Cells

Xiaowei Zhang1,2, Shili Wu3, Yong Zhu3 and Cong-Qiu Chu4,5, 1Oregon Health & Science University, Portland, OR, 2VA Portland Health Care System, Portland, OR, 3VivoScript, Inc, Costa Mesa, CA, 4Rheumatology, Oregon Health & Science University, Portland, OR, 5Rheumatology, VA Portland Health Care System, Portland, OR

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Animal models, cartilage, Mesenchymal stem cells and osteoarthritis

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Session Information

Date: Sunday, October 21, 2018

Session Title: 3S085 ACR Abstract: Osteoarthritis & Joint Biology–Basic Science (846–850)

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Microfracture induces fibrocartilage or fibro-hyaline cartilage both are biomechanically inferior to hyaline cartilage. We reported previously that a super positively charged SOX9 (scSOX9) improved the quality of microfracture induced cartilage repair by inducing mesenchymal stem cell differentiation into chondrocytes and promoting hyaline-like cartilage. Here we examined the long-term efficacy of cartilage repair induced by microfracture with scSOX9 by assessing biomechanical property of the repaired cartilage.    Methods: A cartilage defect was created at the right femoral trochlear groove in New Zealand female rabbits and microfracture was performed. scSOX9 was administered at the site of mcrofracture via a collagen membrane. Cartilage repair was assessed at 12 weeks by gross morphology, histology and matrix components. The distal femur was extirpated for biomechanical test.   Results: Text Box: Figure 1. Mechanical property of repaired cartilage. (A) Thickness of reparative tissue in patellar groove. (B) Mechanical Young’s modulus at 50 μm indentation amplitude of representative control and treated patellar grooves. Data are presented for each region as the averaged of all control (n = 8) and all treated patellar grooves (n = 6-8), *p<0.05 and *** p<0.001 (compared with SOX9 group); # Not significant (compared with SOX9 group). Mem: collagen membrane only; A76E: scSOX9-A76E mutant; SOX9: super positively charged SOX9. Cartilage defect in rabbits was treated with microfracture with collagen membrane only; with a SOX9 mutant, scSOX9-A76E or with scSOX9 respectively. Rabbits were observed for 12 weeks post-surgery. scSOX9 treated group induced hyaline-like cartilage while collagen-membrane only induced fibrocartilage and mutant scSOX9-A76E poorly induced cartilage repair. The cartilage matrix in scSOX9 treated group showed highly enriched proteoglycan content. The thickness of repaired cartilage induced by scSOx9 was comparable to that of normal cartilage in the same area. Whereas, collagen membrane only induced a thinner layer of cartilage, and scSOX9-A76E treated group showed even worse repaired tissue. In consistent with the histological data and the thickness of the repaired cartilage, the mechanical property of scSOX9 induced cartilage was also similar to that of normal cartilage (Figure 1).   Conclusion: This long term in vivo study demonstrated that when administered at the site of microfracture, scSOX9 was able to induce reparative tissue with features of hyaline cartilage and near normal biomechanical properties. scSOX9 induced cartilage repair was endurable in long term. Together, this technology has potential to translate into clinical use for cartilage repair to prevent progression to osteoarthritis.

Disclosure: X. Zhang, None; S. Wu, VivoScript, Inc, 3; Y. Zhu, VivoScript, Inc, 3; C. Q. Chu, VivoScript, Inc, 2.

To cite this abstract in AMA style:

Zhang X, Wu S, Zhu Y, Chu CQ. Long Term Efficacy of Cartilage Repair Induced By scSOX9 in Situ with Bone Marrow-Derived Mesenchymal Stem Cells [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/long-term-efficacy-of-cartilage-repair-induced-by-scsox9-in-situ-with-bone-marrow-derived-mesenchymal-stem-cells/. Accessed February 3, 2023.
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