頁籤選單縮合
題 名 | Protection of Bone Marrow-Derived CD45+/CD34–/lin- Stromal Cells with Immunosuppressant Activity against Ischemia/Reperfusion Injury in Rats |
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作 者 | Chung, Yuan-chang; Ma, Ming-chieh; Huang, Bo-yang; Chiang, Han-sun; Chou, Shiu-huey; | 書刊名 | 中國生理學雜誌 |
卷 期 | 54:3 2011.06[民100.06] |
頁 次 | 頁169-182 |
分類號 | 414.7 |
關鍵詞 | Bone marrow; CD45+ stromal cells; Ischemia/reperfusion; Cardioprotection; Soluble factor; |
語 文 | 英文(English) |
英文摘要 | Non-hematopoietic CD45+ precursor cells are not known to differentiate into cardiomyocytes. We found that CD45+/CD34–/lin– stromal cells isolated from mouse bone marrow (BMSCs) potentially differentiated into cardiomyocyte-like cells in vitro. Therefore, we hypothesized that the CD45+/CD34–/ lin– BMSCs might protect rat hearts against ischemia/reperfusion (IR) injury following xeno-transplantation. In the present study, BMSCs were isolated by immunoselection and their cellular phenotype and biochemical properties were characterized. The immunological inertness of BMSCs was examined by the allogeneic and xenogeneic mixed lymphocyte reaction (MLR). The potential role of BMSCs for cardioprotection was evaluated by intravenous introduction of 1 × 106 cells into rat IR hearts, induced by left coronary ligation for 45 min and released for 72 h. Changes in cardiac contractility and the degree of myocardial injury were assessed. Our findings indicated that BMSCs expressed the muscle-cell marker α-actinin after 5-azacytidine treatment. CD45+/CD34–/lin– stromal cells were characterized as mesenchymal progenitor cells based on the expression of Sca-1 and Rex-1. The MLR assay revealed an immunosuppression of BMSCs on mouse and rat lymphocytes. After xeno-transplantation, the BMSCs engrafted into the infarct area and attenuated IR injury. However, increases in intracardial TGF-β and IFN-γ contents of IR hearts were not affected by BMSC treatment. Interestingly, ex vivo evidence indicated that CXCR4, SDF-1 and TGFβ-1 receptors were up-regulated after the cells were exposed to tissue extracts prepared from rat post-IR hearts. In addition, IFN-γ treatment also markedly increased Sca-1 expression in BMSCs. Mechanistically, these results indicated that CXCR4/SDF-1 and TGF-β signals potentially enhanced the interaction of BMSCs with the damaged myocardium, and increased IFN-γ in post-ischemic hearts might cause BMSC to behave more like stem cells in cardioprotection. These data show that CD45+/ CD34–/lin– BMSCs possess cardioprotective capacity. Evidently, the accurate production of soluble factors TGF-β and IFN-γ in parallel with increased expression of both TGF-β and Sca-1 receptors may favor BMSCs to achieve a more efficient protective capacity. |
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