Stem Cells in Kidney Ischemia: From Inflammation and Fibrosis to Renal Tissue Regeneration

Abstract

Ischemic nephropathy consists of progressive renal function loss due to renal hypoxia, inflammation, microvascular rarefaction, and fibrosis. We provide a literature review focused on kidney hypoperfusion-dependent inflammation and its influence on renal tissue’s ability to self-regenerate. Moreover, an overview of the advances in regenerative therapy with mesenchymal stem cell (MSC) infusion is provided. Based on our search, we can point out the following conclusions: 1. endovascular reperfusion is the gold-standard therapy for RAS, but its success mostly depends on treatment timeliness and a preserved downstream vascular bed; 2. anti-RAAS drugs, SGLT2 inhibitors, and/or anti-endothelin agents are especially recommended for patients with renal ischemia who are not eligible for endovascular reperfusion for slowing renal damage progression; 3.TGF-β, MCP-1, VEGF, and NGAL assays, along with BOLD MRI, should be extended in clinical practice and applied to a pre- and post-revascularization protocols; 4. MSC infusion appears effective in renal regeneration and could represent a revolutionary treatment for patients with fibrotic evolution of renal ischemia.

Human umbilical cord mesenchymal stem cell exosomes alleviate acute kidney injury by inhibiting pyroptosis in rats and NRK-52E cells

“…In such transplant patients, the protection of allograft function is particularly crucial, especially in renal fibrosis after IRI. MSCs can respond to specific triggers with differentiation to mature cells with consequent tissue regeneration [ 23 ]. MSCs could represent a revolutionary treatment for patients with fibrotic evolution.…”

It’s Time for New Insights into Renovascular Hypertension at the Molecular Level

“…Cianci et al [47] have recently published original data on NGAL and circulating renal stem cell (RSC) changes before and after PTRA and stenting in five patients with RAS.…”

“…MSCs ability to migrate and/or differentiate in the kidney following several renal insulting mechanisms defines the extraordinary repairing potentiality of these peculiar cells. Once migrated or activated in the damaged kidney, MSCs produce and release, through extracellular vesicles and exosomes, a variety of cytokines and chemokines able to reduce inflammation and increase different reparative pathways[47] [58]. Some reports in animal models have explored the potential restorative role of stem cells after renal reperfusion and have demonstrated encouraging and promising results[59] [60].…”

Role of MCP-1 as an inflammatory biomarker in nephropathy

“…The main producers of MCP-1 are monocytes and macrophages, although it is also expressed by various other cell types such as endothelial cells, fibroblasts, epithelial cells, smooth muscle cells, mesangial cells, astrocytes, and microglia ( 4 , 5 ). Upon binding to its receptor, MCP-1 can induce homing, migration, activation, differentiation,and development of lymphocytes and NK cells; facilitate infiltration of monocytes and macrophages; promote inflammation occurrence; stimulate angiogenesis; as well as exert fibrotic effects ( 6 ). Studies have demonstrated that MCP-1 plays a significant role in fibrosis affecting multiple organs ( 7 ).…”