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小鼠间充质干细胞表现出功能趋化因子受体的有限库:与人类的比较。

Murine mesenchymal stem cells exhibit a restricted repertoire of functional chemokine receptors: comparison with human.

作者信息

Chamberlain Giselle, Wright Karina, Rot Antal, Ashton Brian, Middleton Jim

机构信息

Leopold Muller Arthritis Research Centre, Medical School, Keele University, RJAH Orthopaedic Hospital, Oswestry, Shropshire, United Kingdom.

出版信息

PLoS One. 2008 Aug 13;3(8):e2934. doi: 10.1371/journal.pone.0002934.

Abstract

Mesenchymal stem cells (MSCs) are non-haematopoeitic, stromal cells that are capable of differentiating into mesenchymal tissues such as bone and cartilage. They are rare in bone marrow, but have the ability to expand many-fold in culture, and retain their growth and multi-lineage potential. The properties of MSCs make them ideal candidates for tissue engineering. It has been shown that MSCs, when transplanted systemically, can home to sites of injury, suggesting that MSCs possess migratory capacity; however, mechanisms underlying migration of these cells remain unclear. Chemokine receptors and their ligands play an important role in tissue-specific homing of leukocytes. Here we define the cell surface chemokine receptor repertoire of murine MSCs from bone marrow, with a view to determining their migratory activity. We also define the chemokine receptor repertoire of human MSCs from bone marrow as a comparison. We isolated murine MSCs from the long bones of Balb/c mice by density gradient centrifugation and adherent cell culture. Human MSCs were isolated from the bone marrow of patients undergoing hip replacement by density gradient centrifugation and adherent cell culture. The expression of chemokine receptors on the surface of MSCs was studied using flow cytometry. Primary murine MSCs expressed CCR6, CCR9, CXCR3 and CXCR6 on a large proportion of cells (73+/-11%, 44+/-25%, 55+/-18% and 96+/-2% respectively). Chemotaxis assays were used to verify functionality of these chemokine receptors. We have also demonstrated expression of these receptors on human MSCs, revealing some similarity in chemokine receptor expression between the two species. Consequently, these murine MSCs would be a useful model to further study the role of chemokine receptors in in vivo models of disease and injury, for example in recruitment of MSCs to inflamed tissues for repair or immunosuppression.

摘要

间充质干细胞(MSCs)是一种非造血性的基质细胞,能够分化为间充质组织,如骨骼和软骨。它们在骨髓中很罕见,但具有在培养中大量扩增的能力,并保留其生长和多谱系分化潜能。MSCs的这些特性使其成为组织工程的理想候选细胞。研究表明,MSCs经全身移植后能够归巢到损伤部位,这表明MSCs具有迁移能力;然而,这些细胞迁移的潜在机制仍不清楚。趋化因子受体及其配体在白细胞的组织特异性归巢中起重要作用。在此,我们确定了来自骨髓的小鼠MSCs的细胞表面趋化因子受体谱,以确定它们的迁移活性。作为比较,我们还确定了来自骨髓的人类MSCs的趋化因子受体谱。我们通过密度梯度离心和贴壁细胞培养从Balb/c小鼠的长骨中分离出小鼠MSCs。通过密度梯度离心和贴壁细胞培养从接受髋关节置换术的患者骨髓中分离出人类MSCs。使用流式细胞术研究MSCs表面趋化因子受体的表达。原代小鼠MSCs在大部分细胞上表达CCR6、CCR9、CXCR3和CXCR6(分别为73±11%、44±25%、55±18%和96±2%)。趋化性分析用于验证这些趋化因子受体的功能。我们还证明了这些受体在人类MSCs上的表达,揭示了这两个物种在趋化因子受体表达上的一些相似性。因此,这些小鼠MSCs将成为一个有用的模型,用于进一步研究趋化因子受体在疾病和损伤体内模型中的作用,例如在将MSCs募集到炎症组织进行修复或免疫抑制方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f18/2488395/9f7e8d878cfc/pone.0002934.g001.jpg

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