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Efficacy and Safety of Human Bone Marrow-Derived Mesenchymal Stem Cells according to Injection Route and Dose in a Chronic Kidney Disease Rat Model
International Journal of Stem Cells
Published online April 30, 2022;  
© 2022 Korean Society for Stem Cell Research.

Han Kyu Chae1, Nayoung Suh2, Myong Jin Jang3, Yu Seon Kim4, Bo Hyun Kim5, Joomin Aum4, Ha Chul Shin6, Dalsan You4, Bumsik Hong5, Hyung Keun Park5, Choung-Soo Kim5

1Department of Urology, Gangneung Asan Medical Center, University of Ulsan College of Medicine, Gangneung, Korea
2Department of Pharmaceutical Engineering, College of Medical Sciences and Department of Medical Sciences, General Graduate School, Soon Chun Hyang University, Asan, Korea
3Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea
4Department of Urology, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
5Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
6Pharmicell Co. Ltd., Seongnam, Korea
Correspondence to: Choung-Soo Kim
Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
Tel: +82-2-3010-3734, Fax: +82-2-477-8928, E-mail: cskim@amc.seoul.kr
*Current Affiliation: Urology Institute, Ehwa Womans University Mokdong Hospital, Seoul, Korea
Received August 26, 2021; Revised February 21, 2022; Accepted March 20, 2022.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Keywords : Chronic kidney disease, Stem cell transplantation, Cell migration, Bone marrow