Affan Asmaa, Al-Jezani Nedaa, Railton Pamela, Powell James N, Krawetz Roman J
McCaig Institute for Bone and Joint Health, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada.
University of Calgary, Biomedical Engineering Graduate Program, Calgary, Canada.
BMC Musculoskelet Disord. 2019 Mar 25;20(1):125. doi: 10.1186/s12891-019-2495-2.
The synovial membrane adjacent to the articular cartilage is home to synovial mesenchymal progenitor cell (sMPC) populations that have the ability to undergo chondrogenesis. While it has been hypothesized that multiple subtypes of stem and progenitor cells exist in vivo, there is little evidence supporting this hypothesis in human tissues. Furthermore, in most of the published literature on this topic, the cells are cultured before derivation of clonal populations. This gap in the literature makes it difficult to determine if there are distinct MPC subtypes in human synovial tissues, and if so, if these sMPCs express any markers in vivo/in situ that provide information in regards to the function of specific MPC subtypes (e.g. cells with increased chondrogenic capacity)? Therefore, the current study was undertaken to determine if any of the classical MPC cell surface markers provide insight into the differentiation capacity of sMPCs.
Clonal populations of sMPCs were derived from a cohort of patients with hip osteoarthritis (OA) and patients at high risk to develop OA using indexed cell sorting. Tri-differentiation potential and cell surface receptor expression of the resultant clones was determined.
A number of clones with distinct differentiation potential were derived from this cohort, yet the most common cell surface marker profile on MPCs (in situ) that demonstrated chondrogenic potential was determined to be CD90/CD44/CD73. A validation cohort was employed to isolate cells with only this cell surface profile. Isolating cells directly from human synovial tissue with these three markers alone, did not enrich for cells with chondrogenic capacity.
Therefore, additional markers are required to further discriminate the heterogeneous subtypes of MPCs and identify sMPCs with functional properties that are believed to be advantageous for clinical application.
与关节软骨相邻的滑膜是滑膜间充质祖细胞(sMPC)群体的所在地,这些细胞具有软骨形成能力。虽然有人推测体内存在多种干细胞和祖细胞亚型,但在人体组织中几乎没有证据支持这一假设。此外,在关于该主题的大多数已发表文献中,细胞在克隆群体衍生之前就进行了培养。文献中的这一空白使得难以确定人类滑膜组织中是否存在不同的MPC亚型,如果存在,这些sMPC在体内/原位是否表达任何能够提供特定MPC亚型功能信息的标志物(例如软骨形成能力增强的细胞)?因此,本研究旨在确定任何经典的MPC细胞表面标志物是否能深入了解sMPC的分化能力。
使用索引细胞分选技术,从一组髋骨关节炎(OA)患者和有OA高风险的患者中获得sMPC的克隆群体。测定所得克隆的三向分化潜能和细胞表面受体表达。
从该队列中获得了许多具有不同分化潜能的克隆,但MPC上(原位)显示软骨形成潜能的最常见细胞表面标志物谱被确定为CD90/CD44/CD73。使用一个验证队列来分离仅具有这种细胞表面谱的细胞。仅用这三种标志物直接从人滑膜组织中分离细胞,并未富集具有软骨形成能力的细胞。
因此,需要额外的标志物来进一步区分MPC的异质亚型,并鉴定具有被认为对临床应用有利的功能特性的sMPC。