Bone marrow-derived mesenchymal stem cells transplantation ameliorates renal injury through anti-fibrotic and anti-inflammatory effects in chronic experimental renovascular disease

Almeida, Aline Gama de; Lira, Rafaelle; Oliveira, Mariana; Martins, Marcela Anjos; Azevedo, Yanca Maiara A. De; Silva, Karina; Carvalho, Simone; Cortez, Erika; Stumbo, Ana Carolina; Carvalho, Laís de; Thole, Alessandra Alves

doi:10.1016/j.bj.2021.07.009

Cited by 13 publications

(9 citation statements)

References 41 publications

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“…Recently, the administration of BMSCs has been shown to accelerate kidney reconstitution[ 28 , 29 ]. However, the underlying mechanism of action of MSCs that promote DKD kidney reconstitution is not yet fully understood.…”

Section: Discussionmentioning

confidence: 99%

Intercellular mitochondrial transfer as a means of revitalizing injured glomerular endothelial cells

Tang¹,

Wei²,

Jiang³

et al. 2022

World J Stem Cells

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BACKGROUND Recent studies have demonstrated that mesenchymal stem cells (MSCs) can rescue injured target cells via mitochondrial transfer. However, it has not been fully understood how bone marrow-derived MSCs repair glomeruli in diabetic kidney disease (DKD). AIM To explore the mitochondrial transfer involved in the rescue of injured glomerular endothelial cells (GECs) by MSCs, both in vitro and in vivo . METHODS In vitro experiments were performed to investigate the effect of co-culture with MSCs on high glucose-induced GECs. The transfer of mitochondria was visua lized using fluorescent microscopy. GECs were freshly sorted and ultimately tested for apoptosis, viability, mRNA expression by real-time reverse transcri ptase-polymerase chain reaction, protein expression by western blot, and mitochondrial function. Moreover, streptozotocin-induced DKD rats were infused with MSCs, and renal function and oxidative stress were detected with an automatic biochemical analyzer and related-detection kits after 2 wk. Kidney histology was analyzed by hematoxylin and eosin, periodic acid-Schiff, and immunohistochemical staining. RESULTS Fluorescence imaging confirmed that MSCs transferred mitochondria to injured GECs when co-cultured in vitro . We found that the apoptosis, proliferation, and mitochondrial function of injured GECs were improved following co-culture. Additionally, MSCs decreased pro-inflammatory cytokines [interleukin (IL)-6, IL-1β, and tumor necrosis factor-α] and pro-apoptotic factors (caspase 3 and Bax). Mitochondrial transfer also enhanced the expression of superoxide dismutase 2, B cell lymphoma-2, glutathione peroxidase (GPx) 3, and mitofusin 2 and inhibited reactive oxygen species (ROS) and dynamin-related protein 1 expression. Furthermore, MSCs significantly ameliorated functional parameters (blood urea nitrogen and serum creatinine) and decreased the production of malondialdehyde, advanced glycation end products, and ROS, whereas they increased the levels of GPx and superoxide dismutase in vivo . In addition, significant reductions in the glomerular basement membrane and renal interstitial fibrosis were observed following MSC treatment. CONCLUSION MSCs can rejuvenate damaged GECs via mitochondrial transfer. Additionally, the improvement of renal function and pathological changes in DKD by MSCs may be related to the mechanism of mitochondrial transfer.

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Section: Discussionmentioning

confidence: 99%

Intercellular mitochondrial transfer as a means of revitalizing injured glomerular endothelial cells

Tang¹,

Wei²,

Jiang³

et al. 2022

World J Stem Cells

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“…This reduction in blood flow stimulates the renin-angiotensin-aldosterone system, leading to increased blood pressure. This model was used to study the mechanisms of hypertension, test the efficacy of antihypertensive therapies ( 116 ), and study the significance of stem cell therapy in the remodeling of fibrotic kidney parenchyma ( 117 ).…”

Section: Surgical Modelsmentioning

confidence: 99%

A review on experimental surgical models and anesthetic protocols of heart failure in rats

et al. 2023

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Heart failure (HF) is a serious health and economic burden worldwide, and its prevalence is continuously increasing. Current medications effectively moderate the progression of symptoms, and there is a need for novel preventative and reparative treatments. The development of novel HF treatments requires the testing of potential therapeutic procedures in appropriate animal models of HF. During the past decades, murine models have been extensively used in fundamental and translational research studies to better understand the pathophysiological mechanisms of HF and develop more effective methods to prevent and control congestive HF. Proper surgical approaches and anesthetic protocols are the first steps in creating these models, and each successful approach requires a proper anesthetic protocol that maintains good recovery and high survival rates after surgery. However, each protocol may have shortcomings that limit the study's outcomes. In addition, the ethical regulations of animal welfare in certain countries prohibit the use of specific anesthetic agents, which are widely used to establish animal models. This review summarizes the most common and recent surgical models of HF and the anesthetic protocols used in rat models. We will highlight the surgical approach of each model, the use of anesthesia, and the limitations of the model in the study of the pathophysiology and therapeutic basis of common cardiovascular diseases.

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“…Almeida et al examined the role of bone-marrow-derived mesenchymal stem cells (MSC) in the remodeling of fibrotic kidney parenchyma. [ 6 ] Renal fibrosis is the common, final outcome of most progressive chronic kidney diseases (CKD). It also serves as a reliable determinant of renal insufficiency.…”

Section: Spotlight On Reviewsmentioning

confidence: 99%

“…Almeida et al showed in a CKD animal model that anti-fibrotic and anti-inflammatory events were orchestrated through transplanted MSCs, reversing renal fibrosis and promoting renal morphological restoration. [ 6 ].…”

Section: Spotlight On Reviewsmentioning

confidence: 99%

An area of greatest vulnerability - Recent advances in kidney injury

Kattner¹

2022

Biomedical Journal

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Bone marrow-derived mesenchymal stem cells transplantation ameliorates renal injury through anti-fibrotic and anti-inflammatory effects in chronic experimental renovascular disease

Cited by 13 publications

References 41 publications

Intercellular mitochondrial transfer as a means of revitalizing injured glomerular endothelial cells

Intercellular mitochondrial transfer as a means of revitalizing injured glomerular endothelial cells

A review on experimental surgical models and anesthetic protocols of heart failure in rats

An area of greatest vulnerability - Recent advances in kidney injury

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