BioImpacts. 2021;11(3): 219-226.
doi: 10.34172/bi.2021.31
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Original Research

Therapeutic effects of bone marrow mesenchymal stem cells via modulation of TLR2 and TLR4 on renal ischemia-reperfusion injury in male Sprague-Dawley rats

Zeinab Karimi 1 ORCID logo, Sahar Janfeshan 1, Elias Kargar Abarghouei 2, Seyedeh-Sara Hashemi 3* ORCID logo

1 Shiraz Nephro-Urology Research Center (SNURC), Shiraz University of Medical Sciences, Shiraz, Iran
2 Department of Anatomical Sciences, Faculty of Medicine, Hormozgan University of Medical Sciences, Hormozgan, Iran
3 Burn and Wound Healing Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Corresponding author: Seydeh Sara Hashemi, Email: sara_hashemi@sums.ac.ir sara_hashemi@sums.ac.ir


Introduction: Acute kidney injury (AKI) induced by renal ischemia-reperfusion (I/R) injury is a pro-inflammatory process that activates toll-like receptors (TLRs). Stem cell therapy holds a great promise for kidney repair. Therefore, we investigated the immunomodulatory role of bone marrow stromal cells (BMSCs) on TLR2 and TLR4 expression in AKI in male Sprague-Dawley rats.
Methods: BMSCs were isolated from the bone marrow of male rats, cultured in DMEM, and characterized using appropriate markers before transplantation. Renal I/R was induced by 45 minutes bilateral ischemia followed by 24 hours of reperfusion. Rats received intraperitoneal injections of BMSCs (1.5 × 106 cells, i.p, per rat) immediately after termination of renal ischemia. Serum samples were collected pre-and post-stem cells injection for assessment of blood urea nitrogen (BUN) and creatinine (Cr) levels. The kidneys were harvested after 24 hours of reperfusion for structural and molecular analysis.
Results: Renal I/R caused severe tissue injuries and increased the level of BUN (166.5 ± 12.9 vs. 18.25 ± 1.75) and Cr (3.7 ± 0.22 vs. 0.87 ± 0.06) compared to the sham group. In addition, mRNA expression of TLR2 and TLR4 elevated in the renal I/R group. Administration of BMSCs improved the functional and structural state of the kidney induced by I/R and down-regulated TLR2 and TLR4 gene expression.
Conclusion: The results showed a highly significant renoprotection by BMSCs that indicates their therapeutic potential in I/R injures. These effects are most likely associated with the TLR2/4 signaling pathway via modulation of the inflammatory response cascades.
Keywords: Bone marrow, Mesenchymal stem cells, Toll-like receptors, Ischemia- reperfusion, Acute kidney injury, Inflammation
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Submitted: 13 Nov 2019
Revision: 04 May 2020
Accepted: 16 May 2020
ePublished: 08 Jul 2020
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