2017 ISAKOS Biennial Congress ePoster #208

 

Self-Assembled, Adhesive Cartilage Gel Using Fetal Cartilage-Derived Progenitor Cells for Cartilage Repair

Byoung-Hyun Min, MD, PhD, Suwon, Gyeonggi-Do KOREA, REPUBLIC OF
Do-Young Park, MD, PhD, Suwon, Gyeonggi-do KOREA, REPUBLIC OF
Jun-Young Chung, MD, Suwon, Gyeonggi-do KOREA, REPUBLIC OF
Doohyung Lee, MD, Prof, Suwon KOREA, REPUBLIC OF
Xiang-Yun Yin, MD, Suwon, Gyeonggi-do KOREA, REPUBLIC OF

Ajou University School of Medicine, Cell therapy center, Suwon-si, Gyeonggi-do, KOREA, REPUBLIC OF

The FDA has not cleared the following pharmaceuticals and/or medical device for the use described in this presentation. The following pharmaceuticals and/or medical device are being discussed for an off-label use:

Summary

We have developed an adhesive, self assembled cartilage gel using fetal cartilage-derived progenitor cells for cartilage repair, which showed to be easy to transplant and effective in a nonhuman primate model

Abstract

Introduction

We hypothesized that fetal cartilage-derived progenitor cells (FCPC) and its extracellular matrix would be useful in repairing focal cartilage defects, considering the previously reported chondrogenic capacity of FCPCs and dynamic repair potential of fetal extracellular matrices. The aim of this study was to develop a self-assembled, FCPC-based cartilage gel for cartilage repair. We first aimed to characterize the cartilage gels during the chondrogenic self-assembly period and optimize the gels in terms of chondrogenesis and adhesiveness. Secondly, we analyzed the in vivo remodeling process for the optimized gels after transplantation in a nude mouse, human cartilage defect model. Finally, we aimed to analyze the long term efficacy, inflammatory reactions, and bio-distribution in a nonhuman primate cartilage defect model.

Methods

Human FCPCs were harvested from 10-13 week old aborti joints. Self-assembled cartilage gels were produced through high density cell culture, followed by chondrogenic induction period of 1, 2, or 3 weeks. Characterization of the gels was done accordingly. The in vivo remodeling process was analyzed at 2, 4, 8 and 12 weeks after transplantation in a nude mouse model. Gels were further transplanted in full thickness cartilage defects of non-human primate knee joints without the use of additional fixation methods. The knee joints were followed with MRI every 8 weeks until 24 weeks after surgery. Repair efficacy was analyzed histologically, while bio-distribution of gels was assessed with human specific ALU sequence genetic analysis and immunohistochemistry. Inflammation was assessed with synovial histology. Statistical analysis was done using Kruskal-Wallis test and Mann Whitney test.

Results

Characterization of the gels according to chondrogenic induction period resulted in increased chondrogenic features over time. Biomechanical properties of adhesive strength and spreadability decreased, while stiffness increased over time. Adhesion strength of the cartilage gels were significantly higher compared to alginate gel controls, with the 2-wk group showing a near 20-fold higher strength (1799.58± 146.37Pa vs. 93.42± 14.71Pa, p<0.001). The in vivo remodeling process of the 2wk cultured gels showed increased cartilage repair characteristics and stiffness over time, with higher integration-failure stress compared to osteochondral autograft controls at 4 weeks (191.01±20.69kPA vs. 69.05±88.25kPA, p<0.01). In the nonhuman primate preclinical investigation, ICRS cartilage repair scores were significantly better in the gel group compared to defects alone after 24 weeks (18; 95%CI16.21-19.79 vs. 8.87; 95%CI6.75-10.98, p<0.001). Biodistribution analysis showed that human cells remained within the transplanted defects only. No significant differences in terms of synovial inflammation was observed between transplanted and non-transplanted knee joints.

Conclusion

A self-assembled, FCPC-based cartilage gel showed high chondrogenic repair capacity as well as adhesive properties, offering an easy, yet effective means of transplantation for cartilage repair.