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

骨髓来源的单核细胞疗法通过调节炎症、抗氧化和凋亡相关分子加速肾缺血再灌注损伤的恢复

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作者:Felipe Mateus Ornellas, Débora Santos Ornellas, Sabrina Vargas Martini, Raquel Carvalho Castiglione, Grasiella Maria Ventura, Patrícia R Rocco, Bianca Gutfilen, Sergio A de Souza, Christina Maeda Takiya, Marcelo Marcos Morales

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.

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.

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.

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.

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