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

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

doi:10.15283/ijsc21146

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

Int J Stem Cells. 2023 Feb 28;16(1):66-77. doi: 10.15283/ijsc21146. Epub 2022 Apr 30.

Authors

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

Affiliations

¹ Department of Urology, Gangneung Asan Medical Center, University of Ulsan College of Medicine, Gangneung, Korea.
² Department of Pharmaceutical Engineering, College of Medical Sciences and Department of Medical Sciences, General Graduate School, Soon Chun Hyang University, Asan, Korea.
³ Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.
⁴ Department of Urology, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
⁵ Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
⁶ Pharmicell Co. Ltd., Seongnam, Korea.

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: Bone marrow; Cell migration; Chronic kidney disease; Stem cell transplantation.

Grants and funding

Acknowledgments This study was supported by a contribution of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI18C0283).