Presented by: Dalsan You MD,PhD
Department of Urology, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine

Introduction

Treatment using stem cells, a key tool of regenerative medicine, has emerged due to limitations in surgical efforts to reduce ischemic time or premedication during partial nephrectomy. The preclinical study using hypoxic preconditioned allogeneic bone marrow-derived mesenchymal stem cells (HP-BMSCs) to treat renal ischemia-reperfusion injury has shown promising results. The authors conducted a phase 1 clinical trial evaluating the safety and potential efficacy of renal arterial injection of HP-BMSCs to prevent renal ischemia-reperfusion injury-induced acute kidney injury.

Materials

The patients who temporarily blocked blood flow to the kidney and underwent partial nephrectomy for renal tumor were enrolled. The clinical trial protocol was authorized by the Ministry of Food and Drug Safety, Republic of Korea (31769), and approved by the institutional review board of Asan Medical Center, Seoul, Republic of Korea (2018-0438), and conformed to the tenets of the Declaration of Helsinki. The brief study protocol was registered on the Clinical Research Information Service site of the Korea Centers for Disease Control and Prevention (KCT0003417). The primary outcome was the safety of renal arterial injection of HP-BMSCs, and the secondary outcome was the protection of renal function.

Results

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Of the 13 patients screened, 10 were registered in the clinical trial. Of them, eight were injected with HP-BMSCs into the renal artery and completed the clinical trial. Seven patients experienced seventeen treatment-emergent adverse events (TEAEs). None of them experienced serious TEAEs, and all TEAEs were considered not to be related to injection of HP-BMSCs. In addition, no clinical significance was identified related to other safety measures, such as laboratory tests, vital signs, and physical examination. The mean value of serum creatinine increased significantly at 1 month versus baseline (1.04 mg/dL versus 0.91 mg/dL, P = 0.0068). However, there was no statistically significant change until 12 months later.

Conclusion

This phase 1 clinical trial confirmed the safety of HP-BMSCs in patients undergoing partial nephrectomy for renal tumor. The potential efficacy of HP-BMSCs needs to be confirmed by a phase 2 clinical trial including a control group.

Funding

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: HI18C2414).

Co-Authors

Myoung Jin Jang,
Asan Institute for Life Sciences, Asan Medical Center

Joomin Aum,
Department of Urology, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine

Yu Seon Kim,
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.

Nayoung Suh,
Department of Pharmaceutical Engineering, College of Medical Sciences and Department of Medical Sciences, General Graduate School, Soon Chun Hyang University

Choung-Soo Kim,
Department of Urology, Ewha Womans University Mokdong Hospital