De Martino M, Zonta S, Rampino T, Gregorini M, Frassoni F, Piotti G, Bedino G, Cobianchi L, Dal Canton A, Dionigi P, Alessiani M
Chirurgia Epatopancreatica, IRCCS Pol San Matteo e Dipartimento di Scienze Chirurgiche, Università di Pavia, Italy.
Transplant Proc. 2010 May;42(4):1331-5. doi: 10.1016/j.transproceed.2010.03.079.
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.
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。