Repeated administration of adipose-derived mesenchymal stem cells added on beneficial effects of empagliflozin on protecting renal function in diabetic kidney disease rat

Chih‐Chao Yang; Yi-Ling Chen; Pei-Hsun Sung; John Y. Chiang; Chih-Hung Chen; Yi-Chen Li; Hon-Kan Yip

Biomedical Journal (Apr 2024)

Repeated administration of adipose-derived mesenchymal stem cells added on beneficial effects of empagliflozin on protecting renal function in diabetic kidney disease rat

Chih‐Chao Yang,
Yi-Ling Chen,
Pei-Hsun Sung,
John Y. Chiang,
Chih-Hung Chen,
Yi-Chen Li,
Hon-Kan Yip

Affiliations

Chih‐Chao Yang: Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Yi-Ling Chen: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Pei-Hsun Sung: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
John Y. Chiang: Department of Computer Science & Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan; Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University, Kaohsiung, Taiwan
Chih-Hung Chen: Divisions of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Yi-Chen Li: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center of Cell Therapy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Corresponding author. Clinical Medicine Research Center, National Cheng Kung University Hospital, 138, Shengli Rd., Tainan 70403, Taiwan. Tel.: +886 6 2353535#4207.
Hon-Kan Yip: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Department of Nursing, Asia University, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; Corresponding author. Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123, Ta Pei Rd., Niao Sung Distr., Kaohsiung 83301, Taiwan. Tel.: +886 7 7317123#2363.

Journal volume & issue: Vol. 47, no. 2
p. 100613

Abstract

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Background: Diabetic kidney disease (DKD) is one of the most significant public health burdens worldwide. This study explored the renal protections of combined adipose-derived mesenchymal stem cells (ADMSCs) and empagliflozin (EMPA) in DKD rats. Methods: Adult-male-SD rats were equally allocated into group 1 (sham-operated-control), group 2 (DKD), group 3 (DKD + EMPA/20 mg/kg/day since day-14 after CKD-induction), group 4 [DKD + ADMSCs (6.0 × 105/intrarenal-arterial-injection/post-day-28, followed by 1.2 × 106/intravenous injection post-days 35 and 42 after CKD-induction, i.e., defined as repeated administration)] and group 5 (DKD + ADMSCs + EMPA) and kidney was harvested post-day-60 CKD-induction. Results: The result showed that the blood sugar and circulatory levels of BUN/creatinine and the ratio of urine protein/creatinine at day 60 were greatly increased in group 2 as compared the SC (i.e., group 1), significantly increased in groups 3 and 4 than in groups 5, but these parameters showed the similar manner in groups 3 and 4, except for blood sugar that was significantly lower in group 3 than in group 4 (all p < 0.0001). The protein levels of inflammation (NF-κB/FNF-α/MMP-9)/oxidative-stress (NOX-1/NOX-2/oxidized protein/p22-phox)/apoptosis (cleaved-caspase-3/cleaved-PARP/mitochondrial-Bax)/fibrosis (TGF-β/Smad 3)/mitochondrial/DNA-damaged (p-DRP1/γ-H2AX) biomarkers revealed a similar manner of creatinine level among the groups (all p < 0.0001). Kidney injury score/fibrotic area/oxidative-stress score (8-OHdG) and cellular levels of kidney-damaged biomarkers (KIM-1/γ-H2AX) showed a unanimous manner. In contrast, the cellular expressions of podocyte components (ZO-1/synaptopodin) revealed an antithetical manner of creatinine among the groups (all p < 0.0001). Conclusion: Combined ADMSCs-EMPA was superior to just one therapy for protecting kidney function and ultra-structural integrity in DKD rodents.

Published in Biomedical Journal

ISSN: 2319-4170 (Print); 2320-2890 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: https://www.sciencedirect.com/journal/biomedical-journal

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