Safety and efficacy of intravenous infusion of allogeneic cryopreserved mesenchymal stem cells for treatment of chronic kidney disease in cats: results of three sequential pilot studies.
Safety and efficacy of intravenous infusion of allogeneic cryopreserved mesenchymal stem cells for treatment of chronic kidney disease in cats: results of three sequential pilot studies.
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DOI：
10.1186/scrt198
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发表时间：
2013-04-30
影响因子：
7.5
通讯作者：
Dow SW
中科院分区：
文献类型：
--
作者：
Quimby JM;Webb TL;Habenicht LM;Dow SW
间充质干细胞（MSC）的管理已被证明可以改善慢性肾病（CKD）啮齿动物模型的肾功能，部分通过减少肾内炎症和抑制纤维化。猫的CKD的特征在于肾小管间质炎症和纤维化，因此用MSC治疗可能改善这种疾病的肾功能和尿炎症标志物。因此，进行了一系列初步研究，以评估在患有自然发生的CKD的猫中静脉内施用同种异体脂肪来源的MSC（aMSC）的安全性和有效性。参加这些研究的猫每2周接受从健康、年轻、无特定病原体的猫收集的同种异体aMSC的静脉内输注。初步研究1中的猫（6只猫）每次输注接受2 × 106个冷冻保存的aMSC，初步研究2中的猫（5只猫）每次输注接受4 × 106个冷冻保存的aMSC，初步研究3中的猫（5只猫）每次输注接受4 × 106个从冷冻保存的脂肪培养的aMSC。在治疗期间监测血清生化、全血细胞计数、尿分析、尿蛋白、肾小球滤过率和尿细胞因子浓度。通过重复测量方差分析（ANOVA），然后进行Bonferroni校正，对临床参数的变化进行统计学比较。初步研究1中的猫几乎没有aMSC输注的不良反应，并且在研究期间血清肌酐浓度存在统计学显著性降低，但是降低的程度似乎不太可能具有临床相关性。在初步研究2中，aMSC输注在猫中的不良反应包括输注期间呕吐（2/5只猫）和呼吸频率和呼吸努力增加（4/5只猫）。初步研究3中的猫未出现任何不良副作用。在初步研究2和3中，猫的血清肌酐浓度和肾小球滤过率未发生显著变化。给予冷冻保存的aMSC与显著的不良反应相关，并且肾功能参数没有明显的临床相关改善。给予从冷冻保存的脂肪中培养的aMSC与不良反应无关，但也与肾功能参数的改善无关。
Administration of mesenchymal stem cells (MSCs) has been shown to improve renal function in rodent models of chronic kidney disease (CKD), in part by reducing intrarenal inflammation and suppressing fibrosis. CKD in cats is characterized by tubulointerstitial inflammation and fibrosis, and thus treatment with MSCs might improve renal function and urinary markers of inflammation in this disease. Therefore, a series of pilot studies was conducted to assess the safety and efficacy of intravenous administration of allogeneic adipose-derived MSCs (aMSCs) in cats with naturally occurring CKD. Cats enrolled in these studies received an intravenous infusion of allogeneic aMSCs every 2 weeks collected from healthy, young, specific pathogen-free cats. Cats in pilot study 1 (six cats) received 2 × 106 cryopreserved aMSCs per infusion, cats in pilot study 2 (five cats) received 4 × 106 cryopreserved aMSCs per infusion, and cats in pilot study 3 (five cats) received 4 × 106 aMSCs cultured from cryopreserved adipose. Serum biochemistry, complete blood count, urinalysis, urine protein, glomerular filtration rate, and urinary cytokine concentrations were monitored during the treatment period. Changes in clinical parameters were compared statistically by means of repeated measures analysis of variance (ANOVA) followed by Bonferroni’s correction. Cats in pilot study 1 had few adverse effects from the aMSC infusions and there was a statistically significant decrease in serum creatinine concentrations during the study period, however the degree of decrease seems unlikely to be clinically relevant. Adverse effects of the aMSC infusion in cats in pilot study 2 included vomiting (2/5 cats) during infusion and increased respiratory rate and effort (4/5 cats). Cats in pilot study 3 did not experience any adverse side effects. Serum creatinine concentrations and glomerular filtration rates did not change significantly in cats in pilot studies 2 and 3. Administration of cryopreserved aMSCs was associated with significant adverse effects and no discernible clinically relevant improvement in renal functional parameters. Administration of aMSCs cultured from cryopreserved adipose was not associated with adverse effects, but was also not associated with improvement in renal functional parameters.
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影响因子：
2.4
作者：
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