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

被引:53
作者
Ornellas, Felipe Mateus [1 ,2 ]
Ornellas, Debora Santos [1 ]
Martini, Sabrina Vargas [1 ]
Catiglione, Raquel Carvalho [1 ,6 ]
Ventura, Grasiella Maria [4 ]
Rocco, Patricia R. [3 ]
Gutfilen, Bianca
de Souza, Sergio A. [5 ]
Takiya, Christina Maeda [5 ]
Morales, Marcelo Marcos [2 ]
机构
[1] Univ Fed Rio de Janeiro, Lab Cellular & Mol Physiol, Sch Med, Rio De Janeiro, Brazil
[2] Univ Fed Rio de Janeiro, Sch Med, Lab Immunopathol, Rio De Janeiro, Brazil
[3] Univ Fed Rio de Janeiro, Sch Med, Lab Pulm Investigat, Inst Biophys Carlos Chagas Filho, Rio De Janeiro, Brazil
[4] Univ Fed Rio de Janeiro, Confocal Microscopy Unit, Inst Biomed Sci, Sch Med, Rio De Janeiro, Brazil
[5] Univ Fed Rio de Janeiro, Dept Radiol, Sch Med, Rio De Janeiro, Brazil
[6] Univ Estado Rio De Janeiro, Biomed Ctr, Lab Clin & Expt Res Vasc Biol, Rio De Janeiro, Brazil
关键词
Ischemia-reperfusion; Renal; Cellular therapy; Bone marrow; MESENCHYMAL STEM-CELLS; TUBULAR EPITHELIAL-CELLS; GROUP BOX-1 PROTEIN; ISCHEMIA/REPERFUSION INJURY; OXIDATIVE STRESS; HEME OXYGENASE-1; PROXIMAL TUBULE; STROMAL CELLS; KIDNEY; REPAIR;
D O I
10.1159/000471866
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 Tc-99m 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. (C) 2017 The Author(s)Published by S. Karger AG, Basel.
引用
收藏
页码:1736 / 1752
页数:17
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