Identification and Characterization of Canine Ligament Progenitor Cells and Their Extracellular Matrix Niche
Identification and Characterization of Canine Ligament Progenitor Cells and Their Extracellular Matrix Niche
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DOI：
10.1021/acs.jproteome.8b00933
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发表时间：
2019-03-01
影响因子：
4.4
通讯作者：
Canty-Laird, Elizabeth G.
中科院分区：
文献类型：
--
作者：
Lee, Katie J.;Comerford, Eithne J.;Canty-Laird, Elizabeth G.
韧带在人和动物中容易损伤和退变，然而韧带的愈合潜力很差，目前的治疗方案无效。基于干细胞的疗法具有治疗韧带损伤的潜力。本研究旨在确定韧带祖细胞(LPC)群体的特征，并确定能促进LPC存活和功能的特定生态位成分。从犬颅十字韧带中分离出LPCs，并对其进行了克隆形成、多向分化和标志物表达的研究。细胞外基质(ECM)的组成通过代谢标记和质谱学技术的新应用来表征。LPCS表现出克隆性、多能性和干细胞标志物的表达。利用蛋白质组学的方法，在LPC的壁龛中鉴定出了许多不同的胶原蛋白、糖蛋白和蛋白多糖。细胞的代谢标记显示了不同的ECM蛋白组独特的周转情况，表明某些生态位成分对LPC生存和功能的重要性。本研究确定的新合成的生态位成分可用于辅助LPCS的鉴定，并促进其存活率和潜在的韧带修复策略的功能。
Ligaments are prone to injury and degeneration in humans and animals, however the healing potential of ligament is poor and current treatment options ineffective. Stem cell-based therapies hold potential for treatment of ligament injuries. This study aimed to characterize a ligament progenitor cell (LPC) population and to identify specific niche components which could promote the survival and function of LPCs. LPCs were isolated from canine cranial cruciate ligament and characterized for clonogenicity, multipotency and marker expression. The extracellular matrix (ECM) composition was characterized by the novel application of a metabolic labeling and mass spectrometry technique. LPCs demonstrated clonogenicity, multipotency, and stem cell marker expression. A number of different collagens, glycoproteins, and proteoglycans were identified in the LPC niche using proteomics. Metabolic labeling of cells demonstrated unique turnover profiles for distinct ECM protein groups, indicating the importance of certain niche components for LPC survival and function. The newly synthesized niche components identified in this study could be exploited to aid identification of LPCs and to promote their survival and function for potential ligament repair strategies.