The Wnt5a Receptor, Receptor Tyrosine Kinase-Like Orphan Receptor 2, Is a Predictive Cell Surface Marker of Human Mesenchymal Stem Cells with an Enhanced Capacity for Chondrogenic Differentiation.
The Wnt5a Receptor, Receptor Tyrosine Kinase-Like Orphan Receptor 2, Is a Predictive Cell Surface Marker of Human Mesenchymal Stem Cells with an Enhanced Capacity for Chondrogenic Differentiation.
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DOI：
10.1002/stem.2691
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Hollander AP
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文献类型：
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作者：
Dickinson SC;Sutton CA;Brady K;Salerno A;Katopodi T;Williams RL;West CC;Evseenko D;Wu L;Pang S;Ferro de Godoy R;Goodship AE;Péault B;Blom AW;Kafienah W;Hollander AP
多能间充质干细胞（MSCs）在组织工程和再生医学中具有巨大的潜力。然而，到目前为止，它们的临床应用开发受到严重限制，因为它们是具有不同谱系分化和组织形成能力的混合细胞群。在这里，我们确定受体酪氨酸激酶样孤儿受体2（ROR 2）作为细胞表面标记物，由具有增强的软骨形成能力的MSC表达。我们产生了具有不同软骨形成能力的克隆人MSC群体。通过筛选大多数软骨形成克隆中上调的基因来鉴定ROR 2。当从未克隆的群体中分离时，ROR 2 +ve MSC比ROR 2-ve或未分级的MSC显着更具软骨形成性。在绵羊软骨修复模型中，与对照组相比，它们产生了显著更多的缺损填充，而软骨质量没有损失。ROR 2 +ve MSC/血管周围细胞存在于发育中的人软骨、成人骨髓和脂肪组织中。骨关节炎（OA）患者骨髓中的频率显著低于对照组。然而，在分离这些细胞并在体外进行初始扩增后，与对照组相比，来自OA患者的群体中有更高的ROR 2表达。此外，在组织工程测定中，骨关节炎衍生的MSC比来自对照患者的MSC能够更好地形成软骨。我们的结论是，表达高水平ROR 2的MSC提供了一个确定的群体，能够可预测地增强软骨生产。干细胞2017;35：2280-2291
Multipotent mesenchymal stem cells (MSCs) have enormous potential in tissue engineering and regenerative medicine. However, until now, their development for clinical use has been severely limited as they are a mixed population of cells with varying capacities for lineage differentiation and tissue formation. Here, we identify receptor tyrosine kinase‐like orphan receptor 2 (ROR2) as a cell surface marker expressed by those MSCs with an enhanced capacity for cartilage formation. We generated clonal human MSC populations with varying capacities for chondrogenesis. ROR2 was identified through screening for upregulated genes in the most chondrogenic clones. When isolated from uncloned populations, ROR2+ve MSCs were significantly more chondrogenic than either ROR2–ve or unfractionated MSCs. In a sheep cartilage‐repair model, they produced significantly more defect filling with no loss of cartilage quality compared with controls. ROR2+ve MSCs/perivascular cells were present in developing human cartilage, adult bone marrow, and adipose tissue. Their frequency in bone marrow was significantly lower in patients with osteoarthritis (OA) than in controls. However, after isolation of these cells and their initial expansion in vitro, there was greater ROR2 expression in the population derived from OA patients compared with controls. Furthermore, osteoarthritis‐derived MSCs were better able to form cartilage than MSCs from control patients in a tissue engineering assay. We conclude that MSCs expressing high levels of ROR2 provide a defined population capable of predictably enhanced cartilage production. Stem Cells 2017;35:2280–2291
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