Bone Marrow-Derived Mononuclear Cell Therapy Accelerates Renal Ischemia-Reperfusion Injury Recovery by Modulating Inflammatory, Antioxidant and Apoptotic Related Molecules

Cell Physiol Biochem. 2017;41(5):1736-1752. doi: 10.1159/000471866. Epub 2017 Mar 31.

Abstract

Background/aims: We investigated the regenerative capacity of intravenous administration of bone marrow-derived mononuclear cells (BMMCs) in a rat model of bilateral renal ischemia/reperfusion (IR) injury and the involvement of inflammatory anti-inflammatory and other biological markers in this process.

Methods: Rats were subjected to 1h bilateral renal pedicle clamping. BMMCs were injected i.v 1h after reperfusion and tracked by 99mTc and GFP+ BMMCs. Twenty-four hours after reperfusion, renal function and histological changes were evaluated. The mRNA (real time PCR) and protein (ELISA and immuno-staining) expression of biological markers were analyzed.

Results: Renal function and structure improved after infusion of BMMCs in the IR group (IR-C). Labeled BMMCs were found in the kidneys after therapy. The expression of inflammatory and biological markers (TLR-2, TRL-4, RAGE, IL-17, HMGB-1, KIM-1) were reduced and the expression of anti-inflammatory and antioxidant markers (IL-10, Nrf2, and HO-1) were increased in IR-C animals compared with IR untreated animals (IR-S). The apoptotic index diminished and the proliferation index increased in IR-C compared with IR-S.

Conclusion: The results contribute to our understanding of the role of different biological players in morphofunctional renal improvement and cytoprotection in a post-ischemic reperfusion kidney injury model subjected to cellular therapy.

Keywords: Bone marrow; Cellular therapy; Ischemia- reperfusion; Renal.

MeSH terms

  • Allografts
  • Animals
  • Antioxidants / metabolism*
  • Apoptosis Regulatory Proteins / metabolism*
  • Biomarkers / metabolism
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Bone Marrow Transplantation*
  • Female
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / therapy
  • Inflammation Mediators / metabolism*
  • Kidney Diseases* / metabolism
  • Kidney Diseases* / pathology
  • Kidney Diseases* / therapy
  • Rats
  • Rats, Wistar
  • Reperfusion Injury* / metabolism
  • Reperfusion Injury* / pathology
  • Reperfusion Injury* / therapy

Substances

  • Antioxidants
  • Apoptosis Regulatory Proteins
  • Biomarkers
  • Inflammation Mediators