Efficacy and Safety of Human Bone Marrow-Derived Mesenchymal Stem Cells according to Injection Route and Dose in a Chronic Kidney Disease Rat Model.

IF 2.5 4区医学 Q3 CELL & TISSUE ENGINEERING

International journal of stem cells Pub Date : 2023-02-28 DOI:10.15283/ijsc21146

Han Kyu Chae, Nayoung Suh, Myong Jin Jang, Yu Seon Kim, Bo Hyun Kim, Joomin Aum, Ha Chul Shin, Dalsan You, Bumsik Hong, Hyung Keun Park, Choung-Soo Kim

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Abstract

Background and objectives: We compared the efficacy and safety of human bone marrow-derived mesenchymal stem cells (hBMSC), delivered at different doses and via different injection routes in an animal model of chronic kidney disease.

Methods and results: A total of ninety 12-week-old rats underwent 5/6 nephrectomy and randomized among nine groups: sham, renal artery control (RA-C), tail vein control (TV-C), renal artery low dose (RA-LD) (0.5×10⁶ cells), renal artery moderate dose (RA-MD) (1.0×10⁶ cells), renal artery high dose (RA-HD) (2.0×10⁶ cells), tail vein low dose (TV-LD) (0.5×10⁶ cells), tail vein moderate dose (TV-MD) (1.0×10⁶ cells), and tail vein high dose (TV-HD) (2.0×10⁶ cells). Renal function and mortality of rats were evaluated after hBMSC injection. Serum blood urea nitrogen was significantly lower in the TV-HD group at 2 weeks (p<0.01), 16 weeks (p<0.05), and 24 weeks (p<0.01) than in the TV-C group, as determined by one-way ANOVA. Serum creatinine was significantly lower in the TV-HD group at 24 weeks (p<0.05). At 8 weeks, creatinine clearance was significantly higher in the TV-MD and TV-HD groups (p<0.01, p<0.05) than in the TV-C group. In the safety evaluation, we observed no significant difference among the groups.

Conclusions: Our findings confirm the efficacy and safety of high dose (2×10⁶ cells) injection of hBMSC via the tail vein.

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人骨髓间充质干细胞注射途径和剂量对慢性肾病大鼠模型的疗效和安全性。

背景和目的:我们比较了不同剂量和不同注射途径的人骨髓间充质干细胞(hBMSC)在慢性肾脏疾病动物模型中的疗效和安全性。方法与结果:90只12周龄大鼠行5/6肾切除术，随机分为9组:假手术组、肾动脉对照组(RA-C)、尾静脉对照组(TV-C)、肾动脉低剂量组(RA-LD) (0.5×106细胞)、肾动脉中剂量组(RA-MD) (1.0×106细胞)、肾动脉高剂量组(RA-HD) (2.0×106细胞)、尾静脉低剂量组(TV-LD) (0.5×106细胞)、尾静脉中剂量组(TV-MD) (1.0×106细胞)、尾静脉高剂量组(TV-HD) (2.0×106细胞)。观察注射hBMSC后大鼠肾功能及死亡率。结论:我们的研究结果证实了高剂量(2×106细胞)经尾静脉注射hBMSC的有效性和安全性。

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来源期刊

International journal of stem cells Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

5.10

自引率

4.30%

发文量

期刊介绍： International Journal of Stem Cells (Int J Stem Cells), a peer-reviewed open access journal, principally aims to provide a forum for investigators in the field of stem cell biology to present their research findings and share their visions and opinions. Int J Stem Cells covers all aspects of stem cell biology including basic, clinical and translational research on genetics, biochemistry, and physiology of various types of stem cells including embryonic, adult and induced stem cells. Reports on epigenetics, genomics, proteomics, metabolomics of stem cells are welcome as well. Int J Stem Cells also publishes review articles, technical reports and treatise on ethical issues.