Abstract

Although cartilage regeneration technology has achieved clinical breakthroughs, whether auricular chondrocytes (AUCs) represent optimal seed cells to achieve stable cartilage regeneration is not clear. In this study, we systematically explore biological behaviors of human- and goat-derived AUCs during in vitro expansion as well as cartilage regeneration in vitro and in vivo. To eliminate material interference, a cell sheet model was used to evaluate the feasibility of dedifferentiated AUCs to re-differentiate and regenerate cartilage in vitro and in vivo. We found that the dedifferentiated AUCs could re-differentiate and regenerate cartilage sheets under the chondrogenic medium system, and the generated chondrocyte sheets gradually matured with increased in vitro culture time (2, 4, and 8 weeks). After the implantation of cartilage sheets with different in vitro culture times in nude mice, optimal neocartilage was formed in the group with 2 weeks in vitro cultivation. After in vivo implantation, ossification only occurred in the group with goat-regenerated cartilage sheet of 8 weeks in vitro cultivation. These results, which were confirmed in human and goat AUCs, suggest that AUCs are ideal seed cells for the clinical translation of cartilage regeneration under the appropriate culture system and culture condition.

Highlights

  • Cartilage defect repair is a longstanding and internationally recognized clinical problem (Chung and Burdick, 2008)

  • Proliferation Capacity The proliferation capacity was a key indicator to judge whether auricular chondrocytes (AUCs) were aging and whether they could be selected as seed cells to regenerate cartilage

  • Our results indicated that the dedifferentiated AUCs could re-differentiate to form neocartilage in the chondrogenic medium system, and gradually matured with extended in vitro cultivation

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Summary

Introduction

Cartilage defect repair is a longstanding and internationally recognized clinical problem (Chung and Burdick, 2008). Cartilage regeneration based on tissue engineering technology has made significant progress, and even achieved clinical breakthroughs (Zhou et al, 2018). The source of seed cells, a core element of cartilage tissue engineering, continues to be a bottleneck restricting clinical translation of cartilage regeneration technology (Kusuhara et al, 2009). Cartilage regenerated from stem cells is ossified in the subcutaneous microenvironment, which greatly limits its application for the repair of cartilage defects in subcutaneous environments such as ears, nose, and trachea (Dickhut et al, 2009; Richter, 2009; Huey et al, 2012). Auricular chondrocytes (AUCs) represent the most widely used cell sources for cartilage regeneration

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