Mesenchymal Stem Cells Infusion Prevents Acute Cellular Rejection in Rat Kidney Transplantation
Mesenchymal Stem Cells Infusion Prevents Acute Cellular Rejection in Rat Kidney Transplantation
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DOI：
10.1016/j.transproceed.2010.03.079
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发表时间：
2010-05-01
影响因子：
0.9
通讯作者：
Alessiani, M.
中科院分区：
文献类型：
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作者：
De Martino, M.;Zonta, S.;Alessiani, M.
间充质干细胞（MSC）是分化成各种成熟细胞谱系的多能细胞。MSC通过抑制T细胞增殖发挥免疫调节作用。本研究旨在探讨骨髓间充质干细胞（MSC）在大鼠肾移植中的作用。将能够表达绿色荧光蛋白（EGFP）的Sprague-Dawley转基因大鼠（SD）用作MSC供体。在双侧肾切除术后进行同基因（刘易斯Lewis至刘易斯，n = 10）和异基因（Fischer至刘易斯，n = 10）肾移植。5只接受同基因移植的移植大鼠用3 × 10（6）MSC（Or B）处理，而另外5只不接受MSC（Gr A）。5只同种异体移植的大鼠接受了3 × 10（6）MSC（或C），另5只未接受MSC（Gr D）。MSC直接注入移植物的肾动脉。未提供免疫抑制治疗。7天后处死动物。对治疗动物进行肾功能生化分析、组织学（Banff标准）和免疫组织学分析（ED 1+和CD 8+）。与A组和C组相比，MSC改善了B组和D组的肾功能。Or B组和Gr D组的肾小管损害较Or A组和C组轻（P <0.01）。血管炎在A组和C组更为突出（P <0.01）。MSC减少炎性浸润;在Gr B和D中，ED 1+细胞的数量低于Gr A和C（P <0.005），这也观察到CD 8+细胞（P <0.05）。我们的研究表明，MSC的输注通过减少细胞浸润来减轻急性排斥反应的组织学损伤。
Mesenchymal stem cells (MSC) are multipotent cells that differentiate into various mature cell lineages. MSC show immunomodulatory effects by inhibiting T-cell proliferation. We evaluated the effect of the infusion of MSC in rats experimental kidney transplantation. Sprague-Dawley transgenic rats (SD) able to express the green fluorescent protein (EGFP) were used as MSC donors. Syngeneic (Lewis to Lewis, n = 10) and allogeneic (Fischer to Lewis, n = 10) kidney transplantations were performed after bilateral nephrectomy. Five transplanted rats who received syngeneic grafts, were treated with 3 x 10(6) MSC (Or B), while the other 5 did not received MSC (Gr A). Five rats with allogenic grafts received 3 x 10(6) MSC (Or C) and another 5 did not receive MSC (Gr D). The MSC were infused directly into the renal artery of the graft. No immunosuppressive therapy was provided. The animals were killed after 7 days. Biochemical analysis for renal function, histological (Banff criteria) and immunohistological analysis (ED1+ and CD8+) were performed on treated animals. MSC improved kidney function in Gr B and D vs Gr A and C. The tubular damage appeared to be less severe among Or B and Gr D with respect to Or A and C (P < .01). Vasculitis was more accentuated in Gr A and C (P < .01). MSCs reduced the inflammatory infiltrate; in Gr B and D, the number of ED1+ cells was lower than in Gr A and C (P < .005), which was also observed for CD8+ cells (P < .05). Our study demonstrated that the infusion of MSC attenuated histological damage from acute rejection by reducing the cellular infiltration.