Which Is the Most Suitable and Effective Route of Administration for Mesenchymal Stem Cell-Based Immunomodulation Therapy in Experimental Kidney Transplantation: Endovenous or Arterial?
Which Is the Most Suitable and Effective Route of Administration for Mesenchymal Stem Cell-Based Immunomodulation Therapy in Experimental Kidney Transplantation: Endovenous or Arterial?
复制标题
DOI：
10.1016/j.transproceed.2010.03.081
复制
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：
--
作者：
Zonta, S.;De Martino, M.;Alessiani, M.
免疫调节细胞治疗代表了一个新的观点，控制细胞免疫反应，决定发生急性排斥反应（ACR）在同种异体移植。间充质干细胞（MSC）通过灭活在移植模型中调节组织损伤的T细胞成分来显示免疫调节作用。推测的作用机制是细胞因子网络募集细胞。本研究的目的是测试哪种给药途径（动脉内与静脉内）是在实验性大鼠肾移植中实现免疫调节作用的最有效途径。将在体细胞水平表达增强型绿色荧光蛋白（EGFP）的转基因Sprague-Dawley大鼠（SD）用作MSC供体：在双侧肾切除术后对大鼠进行异基因Fischer至刘易斯移植（每组n = 4）。在Gr B中，将3 × 10（6）MSC输注到移植肾动脉中，而在Gr C中，将它们输注到尾静脉中。未处理的Gr A为对照组。未给予免疫抑制治疗。术后第7天处死动物。对移植动物进行肾功能的生化分析、组织学（Banff标准）和免疫组织学（抗EGFP-免疫球蛋白）分析。在B组中，功能恢复更快（肌酐：B组vs C组，P <0.05）。移植物中的炎性浸润在Gr B组比Gr C组少，保留了肾小管、动脉和肾小球（P <0.01）。动脉内灌注骨髓间充质干细胞能更有效地控制ACR。
Immunomodulating cell therapy represents a new perspective for the control of cellular immune responses that determine the occurrence of acute rejection (ACR) in allotransplantation. Mesenchymal stem cells (MSC) demonstrate immunoregulatory effects by inactivating T-cell components that regulate tissue damage in transplantation models. The presumed mechanism of action is recruitment of cells by a cytokine network. The purpose of this study was to test which route of administartion (intra-arterial vs intravenous) was the most effective route to achieve immunomodulating effects in experimental rat kidney transplantation. Transgenic Sprague-Dawley rats (SD) expressing the enhanced green fluorescent protein (EGFP) at the somatic level were used as MSC donors: Allogeneic Fischer to Lewis grafts (n = 4 per group) were performed in rats after bilateral nephrectomy. In Gr B, 3 x 10(6) MSCs were infused into the renal graft artery, whereas in Gr C, they were infused into the tail vein. The untreated Gr A were a control group. No immunosuppressive therapy was administered. The animals were sacrificed at day 7 postoperatively. Biochemical analysis for renal function, histological (Banff criteria) and immunohistological (anti-EGFP-Immunoglobulin) analysis were performed on the transplanted animals. In Gr B, functional recovery was more rapid (creatinine: Gr B vs Gr C, P < .05). The inflammatory infiltrate in the graft was less in Gr B vs Gr C, with preservation of tubules, arteries, and glomeruli (P < .01). Intra-arterial infusion of MSCs was more effective to control ACR.