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Hypoxic Preconditioned Mesenchymal Stromal Cell Therapy in a Rat Model of Renal Ischemia-reperfusion Injury: Development of Optimal Protocol to Potentiate Therapeutic Efficacy
Int J Stem Cells 2018;11:157-167
Published online November 30, 2018;  
© 2018 Korean Society for Stem Cell Research.

Myoung Jin Jang1,2, Dalsan You2, Jin Young Park3, Kyung Kim3, Joomin Aum2, Chunwoo Lee4, Geehyun Song5, Ha Chul Shin6, Nayoung Suh7, Yong Man Kim6, Choung-Soo Kim2

1Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, 2Department of Urology, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, 3Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, 4Department of Urology, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon, Korea, 5Department of Urology, Kangwon National University Hospital, Chuncheon, Korea, 6Pharmicell Co. Ltd., Seongnam, Korea, 7Department of Pharmaceutical Engineering, College of Medical Sciences, Soon Chun Hyang University, Asan, Korea
Correspondence to: Choung-Soo Kim
Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
Tel: +82-2-3010-3734, Fax: +82-2-477-8928 E-mail: cskim@amc.seoul.kr
Received August 25, 2018; Revised August 28, 2018; Accepted October 12, 2018.
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
Although previous and ongoing clinical studies have used stromal cells during renal ischemia-reperfusion injury (IRI), there is little consensus regarding the optimal protocol. We aimed to optimize the protocol for hypoxic preconditioned human bone marrow-derived mesenchymal stromal cell (HP-hBMSC) therapy in a rat model of renal IRI. We determined the optimal injection route (renal arterial, renal parenchymal, and tail venous injection), dose (low-dose: 1×106, moderate-dose: 2×106, and high-dose: 4×106), and injection period (pre-, concurrent-, and post-IRI). During optimal injection route study, renal arterial injections significantly reduced the decreasing glomerular filtration rate (GFR), as compared to GFRs for the IRI control group, 2 and 4 days after IRI. Therapeutic effects and histological recoveries were the greatest in the group receiving renal arterial injections. During the dose finding study, high-dose injections significantly reduced the decreasing GFR, as compared to GFRs for the IRI control group, 3 days after IRI. Therapeutic effects and histological recoveries were the greatest in the high-dose injection group. While determining the optimal injection timing study, concurrent-IRI injection reduced elevated serum creatinine levels, as compared to those of the IRI control group, 1 day after IRI. Pre-IRI injection significantly reduced the decreasing GFR, as compared with GFRs for the IRI control group, 1 day after IRI. Therapeutic effects and histological recoveries were the greatest in the concurrent-IRI group. In conclusion, the concurrent-IRI administration of a high dose of HP-hBMSC via the renal artery leads to an optimal recovery of renal function after renal IRI.
Keywords : Ischemia-reperfusion injury, Acute kidney injury, Hypoxia preconditioning, Cell therapy, Renal function


November 2018, 11 (2)