Potential Strategies for Kidney Regeneration With Stem Cells: An Overview

Tsuji, Kenji; Kitamura, Shinji; Wada, Jun

doi:10.3389/fcell.2022.892356

Cited by 5 publications

(1 citation statement)

References 55 publications

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“…Single or repeated acute kidney injuries may lead to chronic kidney failure exacerbated by comorbidities, contributions by distal organs, therapeutics, and environmental exposures [ 93 , 94 , 95 ]. Notions of a “renal repair transcriptome” [ 44 ] and “conserved cellular responses to kidney injury” [ 96 ] have been forwarded along with regeneration by potential renal stem cells and tubular progenitors [ 97 , 98 ] to help explain transcriptional responses to kidney injury [ 43 ]. Single nucleus transcriptomics (snRNA-seq) can dissect out small populations of proximal tubule cells that fail to repair and persist after acute kidney injury.…”

Section: Discussionmentioning

confidence: 99%

Insights into Repeated Renal Injury Using RNA-Seq with Two New RPTEC Cell Lines

Merrick,

Martin,

Brooks

et al. 2023

IJMS

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Renal proximal tubule epithelial cells (RPTECs) are a primary site for kidney injury. We created two RPTEC lines from CD-1 mice immortalized with hTERT (human telomerase reverse transcriptase) or SV40 LgT antigen (Simian Virus 40 Large T antigen). Our hypothesis was that low-level, repeated exposure to subcytotoxic levels of 0.25–2.5 μM cisplatin (CisPt) or 12.5–100 μM aflatoxin B1 (AFB1) would activate distinctive genes and pathways in these two differently immortalized cell lines. RNA-seq showed only LgT cells responded to AFB1 with 1139 differentially expressed genes (DEGs) at 72 h. The data suggested that AFB1 had direct nephrotoxic properties on the LgT cells. However, both the cell lines responded to 2.5 μM CisPt from 3 to 96 h expressing 2000–5000 total DEGs. For CisPt, the findings indicated a coordinated transcriptional program of injury signals and repair from the expression of immune receptors with cytokine and chemokine secretion for leukocyte recruitment; robust expression of synaptic and substrate adhesion molecules (SAMs) facilitating the expression of neural and hormonal receptors, ion channels/transporters, and trophic factors; and the expression of nephrogenesis transcription factors. Pathway analysis supported the concept of a renal repair transcriptome. In summary, these cell lines provide in vitro models for the improved understanding of repeated renal injury and repair mechanisms. High-throughput screening against toxicant libraries should provide a wider perspective of their capabilities in nephrotoxicity.

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Section: Discussionmentioning

confidence: 99%

Insights into Repeated Renal Injury Using RNA-Seq with Two New RPTEC Cell Lines

Merrick,

Martin,

Brooks

et al. 2023

IJMS

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Kidney organoids: steps towards better organization and function

Davies,

Holland,

Gül

2024

Biochemical Society Transactions

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Kidney organoids — 3D representations of kidneys made either from pluripotent or tissue stem cells — have been available for well over a decade. Their application could confer notable benefits over longstanding in vivo approaches with the potential for clinically aligned human cells and reduced ethical burdens. They been used, at a proof-of-concept level, in development in disease modeling (including with patient-derived stem cells), and in screening drugs for efficacy/toxicity. They differ from real kidneys: they represent only foetal-stage tissue, in their simplest forms they lack organ-scale anatomical organization, they lack a properly arranged vascular system, and include non-renal cells. Cell specificity may be improved by better techniques for differentiation and/or sorting. Sequential assembly techniques that mimic the sequence of natural development, and localized sources of differentiation-inducing signals, improve organ-scale anatomy. Organotypic vascularization remains a challenge: capillaries are easy, but the large vessels that should serve them are absent from organoids and, even in cultured real kidneys, these large vessels do not survive without blood flow. Transplantation of organoids into hosts results in their being vascularized (though probably not organotypically) and in some renal function. It will be important to transplant more advanced organoids, with a urine exit, in the near future to assess function more stringently. Transplantation of human foetal kidneys, followed by nephrectomy of host kidneys, keeps rats alive for many weeks, raising hope that, if organoids can be produced even to the limited size and complexity of foetal kidneys, they may one day be useful in renal replacement.

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

Cianci

Simeoni

Cianci

et al. 2023

IJMS

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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.

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Potential Strategies for Kidney Regeneration With Stem Cells: An Overview

Cited by 5 publications

References 55 publications

Insights into Repeated Renal Injury Using RNA-Seq with Two New RPTEC Cell Lines

Insights into Repeated Renal Injury Using RNA-Seq with Two New RPTEC Cell Lines

Kidney organoids: steps towards better organization and function

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

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