Reversibly Immortalized Mouse Articular Chondrocytes Acquire Long-Term Proliferative Capability While Retaining Chondrogenic Phenotype

Cell Transplantation

Article

Eric Wagner¹  Richard Rames¹  Joseph D. Lamplot¹  Gaurav Luther¹  Hue H. Luu¹  Lewis L. Shi¹  Sherwin H. Ho¹  Jovito Angeles¹  Rex C. Haydon¹  Fang Deng²  Wenwen Zhang³  Zhan Liao⁴  Guoxin Nan⁵  Wei Shui⁵  Tong-Chuan He⁵  Min Qiao⁵  Liangjun Yin⁵  Hongmei Zhang⁵  Youlin Deng⁵  Zhongliang Wang⁵  Ruidong Li⁵  Zhengjian Yan⁵  Wei Liu⁵  Qian Zhang⁵  Bo Liu⁵  Zhonglin Zhang⁶  Junhui Zhang⁶  Jixing Ye⁷ 

[1] Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA;Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA;Department of Cell Biology, Third Military Medical University, Chongqing, China;Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA;Department of Laboratory Medicine, the Affiliated Hospital, Binzhou Medical University, Yantai, Shandong, China;Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA;Department of Orthopaedic Surgery, Xiang-Ya Hospital of Central South University, Changsha, China;Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA;Department of Orthopaedic Surgery, the First Affiliated Hospital, and Ministry of Education Key Laboratory of Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China;Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA;Department of Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China;Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA;School of Bioengineering, Chongqing University, Chongqing, China;

关键词: Articular cartilage;    Chondrocytes;    Chondrogenesis;    Tissue engineering;    Immortalization;    Chondrogenic progenitors;    Osteoarthritis;   

DOI  :  10.3727/096368914X681054

 received in 2013-08-07, accepted in 2014-04-16,  发布年份 2015

来源: Sage Journals

【 摘 要 】

Cartilage tissue engineering holds great promise for treating cartilaginous pathologies including degenerative disorders and traumatic injuries. Effective cartilage regeneration requires an optimal combination of biomaterial scaffolds, chondrogenic seed cells, and biofactors. Obtaining sufficient chondrocytes remains a major challenge due to the limited proliferative capability of primary chondrocytes. Here we investigate if reversibly immortalized mouse articular chondrocytes (iMACs) acquire long-term proliferative capability while retaining the chondrogenic phenotype. Primary mouse articular chondrocytes (MACs) can be efficiently immortalized with a retroviral vector-expressing SV40 large T antigen flanked with Cre/loxP sites. iMACs exhibit long-term proliferation in culture, although the immortalization phenotype can be reversed by Cre recombinase. iMACs express the chondrocyte markers Col2a1 and aggrecan and produce chondroid matrix in micromass culture. iMACs form subcutaneous cartilaginous masses in athymic mice. Histologic analysis and chondroid matrix staining demonstrate that iMACs can survive, proliferate, and produce chondroid matrix. The chondrogenic growth factor BMP2 promotes iMACs to produce more mature chondroid matrix resembling mature articular cartilage. Taken together, our results demonstrate that iMACs acquire long-term proliferative capability without losing the intrinsic chondrogenic features of MACs. Thus, iMACs provide a valuable cellular platform to optimize biomaterial scaffolds for cartilage regeneration, to identify biofactors that promote the proliferation and differentiation of chondrogenic progenitors, and to elucidate the molecular mechanisms underlying chondrogenesis.

【 授权许可】

Unknown   
© 2015 Cognizant Comm. Corp.

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