Lim Chae-Young, Han Jae-Ik, Kim Seung-Gon, Lee Chang-Min, Park Hee-Myung
Am J Vet Res. 2016 Feb;77(2):208-17. doi: 10.2460/ajvr.77.2.208.
To evaluate the usefulness of autologous bone marrow-derived mesenchymal stem cell (BM-MSC) therapy for the treatment of dogs with experimentally induced acute kidney injury.
6 healthy dogs.
After induction of kidney injury (day 0) with cisplatin (5 mg/kg, IV), dogs immediately received saline (0.9% NaCl) solution (10 mL; n = 3) or BM-MSCs (1 × 10(6) cells/kg in 10 mL of saline solution; 3) IV. A CBC, serum biochemical analysis, and urinalysis were performed for each dog before administration of cisplatin and on days 1 through 4. Glomerular filtration rate was determined for all dogs on days -7 and 2; BM-MSC tracking by MRI was performed on BM-MSC-treated dogs on days -14 and 4. After sample collection and BM-MSC tracking on day 4, all dogs were euthanized; kidney tissue samples underwent histologic evaluation, immunohistochemical analysis, and cytokine profiling via reverse transcriptase PCR assays.
Kidney tissue from both groups had mononuclear inflammatory cell infiltration, tubular necrosis, dilated tubules, and glomerular damage. However, there was less fibrotic change and increased proliferation of renal tubular epithelial cells in the BM-MSC-treated dogs, compared with findings for the control dogs. Expressions of tumor necrosis factor-α and transforming growth factor-β were lower in the BM-MSC-treated group, compared with findings for the control group. Laboratory data revealed no improvement in the renal function in BM-MSC-treated dogs.
Results of this study suggested that autologous BM-MSCs may accelerate renal regeneration after experimentally induced acute kidney injury in dogs.
评估自体骨髓间充质干细胞(BM-MSC)疗法对实验性诱导急性肾损伤犬的治疗效果。
6只健康犬。
用顺铂(5毫克/千克,静脉注射)诱导肾损伤(第0天)后,犬立即静脉注射生理盐水(0.9%氯化钠)溶液(10毫升;n = 3)或BM-MSCs(1×10⁶个细胞/千克,溶于10毫升生理盐水溶液中;n = 3)。在给予顺铂前以及第1至4天,对每只犬进行全血细胞计数、血清生化分析和尿液分析。在第-7天和第2天测定所有犬的肾小球滤过率;在第-14天和第4天,对接受BM-MSC治疗的犬进行MRI追踪BM-MSC。在第4天采集样本并进行BM-MSC追踪后,对所有犬实施安乐死;对肾组织样本进行组织学评估、免疫组化分析以及通过逆转录酶PCR测定细胞因子谱。
两组的肾组织均有单核炎性细胞浸润、肾小管坏死、肾小管扩张和肾小球损伤。然而,与对照组犬相比,接受BM-MSC治疗的犬纤维化改变较少,肾小管上皮细胞增殖增加。与对照组相比,BM-MSC治疗组肿瘤坏死因子-α和转化生长因子-β的表达较低。实验室数据显示,接受BM-MSC治疗的犬肾功能无改善。
本研究结果表明,自体BM-MSCs可能会加速实验性诱导急性肾损伤犬的肾脏再生。