Tissue-Specific Progenitor and Stem Cells Human Cartilage-Derived Progenitor Cells From Committed Chondrocytes for Efficient Cartilage Repair and Regeneration-猫眼课题宝

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2016

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Yangzi Jiang;Youzhi Cai;Wei Zhang-;Zi Yin;Changchang Hu;Tong Tong-Tong;Ping Lu;Shufang Zhang;D. Neculai;R. Tuan;H. Ouyang

关节软骨在生理上不是一种自我更新的组织。软骨损伤常从关节面发展到软骨下骨，导致组织退行性疾病的发病机制，如骨关节炎。利用自体软骨细胞为基础的组织工程治疗软骨缺损的方法已经发展和使用了20多年；然而，软骨细胞体外扩增的挑战仍然存在。软骨干细胞/祖细胞（CSPCs）是一种很有前景的细胞来源，近年来引起了人们的关注。由于它们的来源和身份尚不清楚，cspc的应用潜力正在积极研究中。在这里，我们发现了一组来源于成人软骨细胞的干细胞/祖细胞的出现，其中成熟软骨细胞标记物COL2和间充质基质/干细胞（MSC）标记物CD146的表达发生了动态变化。这些细胞被称为软骨细胞衍生祖细胞（CDPCs）。在培养过程中，通过物理生化指标确定CDPCs的干细胞样潜能和分化状态。低密度低糖二维培养条件（2DLL）是CDPCs出现和增殖增强的关键条件。CDPCs表现出与骨髓间充质基质/干细胞相似的表型，但表现出更大的成软骨潜能。此外，2dll培养的CDPCs在体外和体内均能有效形成软骨，并在15例患者中修复大膝关节软骨缺损（6-13 cm）。这些发现提示了软骨细胞和CDPCs之间的表型转换，并提供了促进这种转换的条件。这些见解扩大了我们对软骨生物学的理解，并可能提高基于软骨细胞的治疗的成功。干细胞转化医学2016；5:733 - 744

Articular cartilage is not a physiologically self-renewing tissue. Injury of cartilage often progresses from the articular surface to the subchondral bone, leading to pathogenesis of tissue degenerative diseases, such as osteoarthritis. Therapies to treat cartilage defects using autologous chondrocytebased tissue engineering have been developed and used for more than 20 years; however, the challenge of chondrocyte expansion in vitro remains. A promising cell source, cartilage stem/progenitor cells (CSPCs), has attracted recent attention. Because their origin and identity are still unclear, the application potential of CSPCs is under active investigation. Here we have captured the emergence of a group of stem/progenitor cells derived from adult human chondrocytes, highlighted by dynamic changes in expression of themature chondrocytemarker, COL2, andmesenchymal stromal/stem cell (MSC)marker, CD146. These cells are termed chondrocyte-derived progenitor cells (CDPCs). The stem cell-like potency and differentiation status of CDPCs were determined by physical and biochemical cues during culture. A low-density, low-glucose 2-dimensional culture condition (2DLL) was critical for the emergence and proliferation enhancement of CDPCs. CDPCs showed similar phenotype as bone marrowmesenchymal stromal/stem cells but exhibited greater chondrogenic potential. Moreover, the 2DLL-cultured CDPCs proved efficient in cartilage formation both in vitro and in vivo and in repairing large knee cartilage defects (6–13 cm) in 15 patients. These findings suggest a phenotype conversion between chondrocytes and CDPCs and provide conditions that promote the conversion. These insights expand our understanding of cartilage biology and may enhance the success of chondrocyte-based therapies. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:733–744

Tissue-Specific Progenitor and Stem Cells Human Cartilage-Derived Progenitor Cells From Committed Chondrocytes for Efficient Cartilage Repair and Regeneration

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