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间充质干细胞输注可预防大鼠肾移植中的急性细胞排斥反应。

Mesenchymal stem cells infusion prevents acute cellular rejection in rat kidney transplantation.

作者信息

De Martino M, Zonta S, Rampino T, Gregorini M, Frassoni F, Piotti G, Bedino G, Cobianchi L, Dal Canton A, Dionigi P, Alessiani M

机构信息

Chirurgia Epatopancreatica, IRCCS Pol San Matteo e Dipartimento di Scienze Chirurgiche, Università di Pavia, Italy.

出版信息

Transplant Proc. 2010 May;42(4):1331-5. doi: 10.1016/j.transproceed.2010.03.079.

Abstract

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 (Gr B), while the other 5 did not received MSC (Gr A). Five rats with allogenic grafts received 3 x 10(6) MSC (Gr 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 Gr B and Gr D with respect to Gr 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.

摘要

间充质干细胞(MSC)是能够分化为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。我们评估了在大鼠实验性肾移植中输注MSC的效果。能够表达绿色荧光蛋白(EGFP)的Sprague-Dawley转基因大鼠(SD)被用作MSC供体。在双侧肾切除术后进行同基因(Lewis到Lewis,n = 10)和异基因(Fischer到Lewis,n = 10)肾移植。五只接受同基因移植的大鼠接受3×10⁶个MSC治疗(B组),而另外五只未接受MSC治疗(A组)。五只接受异基因移植的大鼠接受3×10⁶个MSC治疗(C组),另外五只未接受MSC治疗(D组)。将MSC直接注入移植肾的肾动脉。未提供免疫抑制治疗。7天后处死动物。对治疗后的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(ED1⁺和CD8⁺)。与A组和C组相比,B组和D组的肾功能得到改善。与A组和C组相比,B组和D组的肾小管损伤似乎不那么严重(P <.01)。A组和C组的血管炎更为明显(P <.01)。MSC减少了炎症浸润;在B组和D组中,ED1⁺细胞的数量低于A组和C组(P <.005),CD8⁺细胞也观察到这种情况(P <.05)。我们的研究表明,输注MSC通过减少细胞浸润减轻了急性排斥反应的组织学损伤。

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