International Journal of Stem Cells

Korean Society for Stem Cell Research (한국줄기세포학회)
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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

  • Han Kyu Chae (Department of Urology, Gangneung Asan Medical Center, University of Ulsan College of Medicine) ;
  • Nayoung Suh (Department of Pharmaceutical Engineering, College of Medical Sciences and Department of Medical Sciences, General Graduate School, Soon Chun Hyang University) ;
  • Myong Jin Jang (Asan Institute for Life Sciences, Asan Medical Center) ;
  • Yu Seon Kim (Department of Urology, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Bo Hyun Kim (Department of Urology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Joomin Aum (Department of Urology, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Ha Chul Shin (Pharmicell Co. Ltd.) ;
  • Dalsan You (Department of Urology, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Bumsik Hong (Department of Urology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Hyung Keun Park (Department of Urology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Choung-Soo Kim (Department of Urology, Asan Medical Center, University of Ulsan College of Medicine)
  • Received : 2021.08.26
  • Accepted : 2022.03.20
  • Published : 2023.02.28
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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.

Keywords

Acknowledgement

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). We thank the Comparative Pathology Core facility at the ConveRgence mEDIcine research cenTer (CREDIT), Asan Medical Center for evaluating the serum BUN, serum creatinine, urine creatinine and urine total protein.

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