The endothelial-to-mesenchymal transition and endothelial cilia in EPC-mediated postischemic kidney protection

Patschan, Daniel; Schwarze, Katrin; Henze, Elvira; Patschan, Susann; Müller, Gerhard A.

doi:10.1152/ajprenal.00306.2015

Cited by 25 publications

(23 citation statements)

References 35 publications

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“…Among those were melatonin [47], 8-O-cAMP [51], Bone Morphogenetic Protein-5 (BMP-5) [46], and Angiopoietin-1 [50] and -2 [49]. A more recent study showed that PACs administration post-AKI did not only prevent the kidney from acute loss of excretory function but also stabilizeed certain structural outcome parameters such as interstitial fibrosis and loss of peritubular capillaries [52]. PACs predominantly act by indirect mechanims, whereas ECFCs also operate as substitutes of damaged endothelial cells [37].…”

Section: Proangiogenic Cells (Pacs) and Endothelial Colony Forming Cementioning

confidence: 99%

Cell-Based Therapies in Acute Kidney Injury (AKI)

Patschan

Buschmann

Ritter

et al. 2018

Kidney Blood Press Res

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Acute kidney injury frequently occurs in hospitalized patients all over the world. The prognosis remains poor since specific therapies for promoting kidney regeneration/repair are still missing. In recent years cell-based strategies have improved AKI outcomes under experimental circumstances. Four groups of cells, each of them displaying certain biological and functional characteristics have been evaluated in AKI, induced Pluripotent Stem Cells (iPSCs), Spermatagonial Stem Cells (SSCs), Proangiogenic Cells (PACs) and Endothelial Colony Forming Cells (ECFCs), and Mesenchymal Stem Cells (MSCs). All of these have been documented to stabilize either parameters of kidney excretory dysfunction and/or certain morphological parameters. The mechanisms responsible for AKI protection include direct (cell incorporation) and indirect processes, the latter being mediated by humoral factors and particularly by the production of so-called extracellular vesicles. Cell-derived vesicular organelles have been shown to carry pro-regenerative micro-RNA molecules which stabilize the vascular and tubular function. The first trials in humans have been initiated, the majority of such trials employs MSCs. However, any transfer of cell-based strategies in the clinical practice is potentially associated with significant difficulties. These include cell availability, tolerance and competence. The article intends to summarize essential informations about all of the four populations mentioned above and to discuss implications for the management of human AKI.

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Section: Proangiogenic Cells (Pacs) and Endothelial Colony Forming Cementioning

confidence: 99%

Cell-Based Therapies in Acute Kidney Injury (AKI)

Patschan

Buschmann

Ritter

et al. 2018

Kidney Blood Press Res

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“…Figure 2 summarizes the EndoMT analyzes. In addition, we quantified interstitial matrix deposition in all groups after masson trichrome staining as published previously [14,19]. Matrix accumulation did not significantly differ between the control and any of the respective postischemic groups or between ´IRI´ and one or more of the interventional groups.…”

Section: Early Mesenchymal Transdifferentiation Of Endothelial Cells mentioning

confidence: 98%

“…We previously discussed reduced endothelial alpha-Tubulin (aT) expression to reflect an endogenous process of self-defense [14]. It needs however to be mentioned that respective analyzes were performed several weeks after IRI (1, 4, and 6 weeks).…”

Section: Endothelial Alpha-tubulin Abundances Do Not Vary Early Aftermentioning

confidence: 99%

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PAC-mediated AKI protection is critically mediated but does not exclusively depend on cell-derived microvesicles

Dihazi¹,

Schwarze²,

Patschan³

et al. 2020

Preprint

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Acute Kidney Injury (AKI) significantly worsens the prognosis of hospitalized patients. In recent years, cell-based strategies have been established as reliable option for improving AKI outcomes in experimental AKI. Own studies focused on so-called Proangiogenic Cells (PACs). Mechanisms that contribute to PAC-mediated AKI protection include production / secretion of extracellular vesicles (MV -microvesicles). In addition, the cells most likely act by paracrinic processes (secretome). The current study evaluated whether AKI may be preventable by the administration of either PAC-derived MV and / or the secretome alone. AKI was induced in male C57/Bl6N mice (8-12 weeks) by bilateral renal ischemia (IRI -40 minutes). Syngeneic murine PACs were stimulated with either melatonine, Angiopoietin-1 or -2, or with Bone Morphogenetic Protein-5 (BMP-5) for one hour, respectively. PACderived MV and the vesicle-depleted supernatant were subsequently collected and i.v. injected postischemia. Mice were analyzed 48 hours later. IRI induced significant kidney excretory dysfunction as reflected by higher serum cystatin C levels. The only measure that improved AKI was the injection of MV, collected from native PACs. The following conditions worsened post-ischemic renal function even further: MV+Ang-1, MV+BMP-5, MV+melatonin, and MV+secretome+Ang-1. Together, our data show that PAC-mediated AKI protection substantially depends on the availability of cell-derived MV. However, since previous data showed improved AKI-protection by PACs after cell preconditioning with certain mediators (Ang-1 and -2, melatonine, BMP-5), other than exclusively vesicle-dependent mechanisms must be involved in PAC-mediated AKI protection.

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“…In an ischemic AKI model by Pastchan et al [74], systemic injection of early EPCs decreased serum creatinine and ameliorated interstitial fibrosis. Exposure of endothelial cells to early EPC supernatant led to decreased smooth muscle actin and tubulin expression.…”

Section: Epc Studies In Various Disease Modelsmentioning

confidence: 99%

Endothelial Progenitor Cells and Kidney Diseases

Özkök

Yildiz

2018

Kidney Blood Press Res

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Endothelial progenitor cells (EPC) are bone marrow derived or tissue-resident cells that play major roles in the maintenance of vascular integrity and repair of endothelial damage. Although EPCs may be capable of directly engrafting and regenerating the endothelium, the most important effects of EPCs seem to be depended on paracrine effects. In recent studies, specific microvesicles and mRNAs have been found to mediate the pro-angiogenic and regenerative effects of EPCs on endothelium. EPC counts have important prognostic implications in cardiovascular diseases (CVD). Uremia and inflammation are associated with lower EPC counts which probably contribute to increased CVD risks in patients with chronic kidney disease. Beneficial effects of the EPC therapies have been shown in studies performed on different models of CVD and kidney diseases such as acute and chronic kidney diseases and glomerulonephritis. However, lack of a clear definition and specific marker of EPCs is the most important problem causing difficulties in interpretation of the results of the studies investigating EPCs.

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The endothelial-to-mesenchymal transition and endothelial cilia in EPC-mediated postischemic kidney protection

Cited by 25 publications

References 35 publications

Cell-Based Therapies in Acute Kidney Injury (AKI)

Cell-Based Therapies in Acute Kidney Injury (AKI)

PAC-mediated AKI protection is critically mediated but does not exclusively depend on cell-derived microvesicles

Endothelial Progenitor Cells and Kidney Diseases

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