Human Cartilage-Derived Progenitor Cells From Committed Chondrocytes for Efficient Cartilage Repair and Regeneration.
Human Cartilage-Derived Progenitor Cells From Committed Chondrocytes for Efficient Cartilage Repair and Regeneration.
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来自定型软骨细胞的人软骨来源的祖细胞，用于有效的软骨修复和再生
DOI：
10.5966/sctm.2015-0192
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发表时间：
2016-06
影响因子：
6
通讯作者：
Ouyang HW
中科院分区：
文献类型：
--
作者：
Jiang Y;Cai Y;Zhang W;Yin Z;Hu C;Tong T;Lu P;Zhang S;Neculai D;Tuan RS;Ouyang HW
软骨干细胞/祖细胞群可来源于完全分化的软骨细胞，其具有重新表达其软骨细胞表型以实现有效软骨再生的潜力。这一新的概念支持使用体外扩增的软骨细胞衍生的祖细胞进行关节修复的可能性。关节软骨不是生理上自我更新的组织。软骨的损伤通常从关节表面进展到软骨下骨，导致组织退行性疾病的发病机制，例如骨关节炎。使用基于自体软骨细胞的组织工程治疗软骨缺损的疗法已经开发和使用了20多年;然而，体外软骨细胞扩增的挑战仍然存在。软骨干/祖细胞（CSPC）是一种很有前途的细胞来源，近年来引起了人们的关注。由于其来源和身份尚不清楚，CSPC的应用潜力正在积极调查中。在这里，我们已经捕获了一组来自成人软骨细胞的干细胞/祖细胞的出现，突出显示了成熟软骨细胞标志物COL 2和间充质基质/干细胞（MSC）标志物CD 146表达的动态变化。这些细胞被称为软骨细胞衍生的祖细胞（CDPC）。CDPCs的干细胞样能力和分化状态由培养过程中的物理和生化线索决定。低密度、低糖二维培养条件（2DLL）是CDPC出现和增殖增强的关键。CDPCs表现出与骨髓间充质干细胞相似的表型，但具有更大的软骨形成潜力。此外，2DLL培养的CDPC在体外和体内均被证明在软骨形成中有效，并且在15名患者中修复大的膝关节软骨缺损（6-13 cm 2）。这些发现表明软骨细胞和CDPC之间的表型转换，并提供促进转换的条件。这些见解扩展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率。软骨是一种不能自我修复的组织，其损伤常常发展为退行性关节疾病的发病机制，例如骨关节炎。虽然组织来源的干细胞已被证明有助于组织更新和体内平衡，但在成人关节软骨中发现的干/祖细胞的来源、生物学功能和应用潜力尚不完全清楚。本研究报告了在特定培养条件下从完全分化的软骨细胞中衍生出软骨干/祖细胞群体，其具有重新表达其软骨细胞表型以实现有效软骨再生的潜力。这些发现支持了使用体外扩增的软骨细胞来源的祖细胞进行关节软骨修复的可能性。
A population of cartilage stem/progenitor cells can be derived from fully differentiated chondrocytes that have the potential to reassume their chondrocytic phenotype for efficient cartilage regeneration. This novel concept supports the possibility of using in vitro amplified chondrocyte-derived progenitor cells for joint repair. 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 chondrocyte-based 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 the mature chondrocyte marker, COL2, and mesenchymal 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 marrow mesenchymal 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 cm2) 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. Injury of cartilage, a non-self-repairing tissue, often progresses to pathogenesis of degenerative joint diseases, such as osteoarthritis. Although tissue-derived stem cells have been shown to contribute to tissue renewal and homeostasis, the derivation, biological function, and application potential of stem/progenitor cells found in adult human articular cartilage are incompletely understood. This study reports the derivation of a population of cartilage stem/progenitor cells from fully differentiated chondrocytes under specific culture conditions, which have the potential to reassume their chondrocytic phenotype for efficient cartilage regeneration. These findings support the possibility of using in vitro amplified chondrocyte-derived progenitor cells for joint cartilage repair.