Advances in stem cell therapy for peritoneal fibrosis: from mechanisms to therapeutics

Huang, Weiyan; Xia, Demeng; Bi, Wendi; Lai, Xueli; Yu, Bing; Chen, Wei

doi:10.1186/s13287-023-03520-3

Cited by 2 publications

(5 citation statements)

References 131 publications

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“…Stem cells (SCs) can differentiate into any cell of the human body and are responsible for the development and regeneration of organs and tissues. SCs may influence cellular differentiation and exert immune regulation and cellular repair effects [ 115 ], and their therapeutic potential has been investigated in several pathologies including peritoneal inflammation and fibrosis, mesenchymal SCs (MSCs) being the most extensively studied [ 116 ]. In vitro and in vivo studies showed that MSCs might represent a novel and effective treatment of PF, mainly through paracrine activity to accelerate healing or differentiation into functional repair cells [ 115 ].…”

Section: Combating Pd-solution Associated Toxicitymentioning

confidence: 99%

“…SCs may influence cellular differentiation and exert immune regulation and cellular repair effects [ 115 ], and their therapeutic potential has been investigated in several pathologies including peritoneal inflammation and fibrosis, mesenchymal SCs (MSCs) being the most extensively studied [ 116 ]. In vitro and in vivo studies showed that MSCs might represent a novel and effective treatment of PF, mainly through paracrine activity to accelerate healing or differentiation into functional repair cells [ 115 ]. In a uremic rat PF model, intravenous injection of adipose-derived MSCs displayed anti-inflammatory (avoidance of leukocyte infiltration and overexpression of inflammatory cytokines including IL-1, IL-6, and TNF-alpha) and anti-fibrotic (regulation of TGF-beta, collagen, and fibronectin) effects in the PM [ 117 ].…”

Section: Combating Pd-solution Associated Toxicitymentioning

confidence: 99%

“…SC therapy has great potential as a new strategy for alleviating PF. However, approaches for treatment are not yet standardized and there is no consensus as to the transplantation protocol [ 115 ]. Thus, further research is needed to define the application of SC therapies in the clinical practice of PD.…”

Section: Combating Pd-solution Associated Toxicitymentioning

confidence: 99%

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Coupling Osmotic Efficacy with Biocompatibility in Peritoneal Dialysis: A Stiff Challenge

Bonomini,

Masola,

Monaco

et al. 2024

IJMS

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Peritoneal dialysis (PD) is a home-based efficacious modality for the replacement of renal function in end-stage kidney failure patients, but it is still under-prescribed. A major limitation is the durability of the dialytic technique. Continuous exposure of the peritoneum to bioincompatible conventional glucose-based solutions is thought to be the main cause of the long-term morpho-functional peritoneal changes that eventually result in ultrafiltration failure. Poor PD solution biocompatibility is primarily related to the high glucose content, which is not only detrimental to the peritoneal membrane but has many potential metabolic side effects. To improve the clinical outcome and prolong the survival of the treatment, PD-related bioincompatibility urgently needs to be overcome. However, combining dialytic and osmotic efficacy with a satisfactory biocompatible profile is proving to be quite difficult. New approaches targeting the composition of the PD solution include the replacement of glucose with other osmotic agents, and the addition of cytoprotective or osmo-metabolic compounds. Other strategies include the infusion of mesenchymal cells or the administration of orally active agents. In the present article, we review the current evidence on efforts to improve the biocompatible and functional performance of PD, focusing on studies performed in vivo (animal models of PD, human subjects on PD).

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Section: Combating Pd-solution Associated Toxicitymentioning

confidence: 99%

Section: Combating Pd-solution Associated Toxicitymentioning

confidence: 99%

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Coupling Osmotic Efficacy with Biocompatibility in Peritoneal Dialysis: A Stiff Challenge

Bonomini,

Masola,

Monaco

et al. 2024

IJMS

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“…These changes impair the function of the PM as a dialysis membrane. Mesothelial–mesenchymal transition (MMT) is a key mechanism that contributes to development of PF by generating fibroblasts and myofibroblasts from PMCs ( Huang et al, 2023 ). MMT is a physiological process that generates fibroblasts and related cells from mesothelial cells to repair damaged tissues.…”

Section: Introductionmentioning

confidence: 99%

“…This process is normally self-limiting and stops when the injury is resolved. However, under persistent stimuli, MMT can become pathological and lead to excessive fibroblast proliferation and tissue fibrosis ( Huang et al, 2023 ). TGF-β1 is involved in the differentiation of PMFBs of resident fibroblasts and also in the mesenchymal conversion of endothelial cells via endothelial-to-mesenchymal transition (EnMT), which call forth to target vasculopathy for the abrogation of fibrosis ( Zeisberg et al, 2007 ; Zeisberg et al, 2008 ; Li et al, 2009 ; Beyer et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Unravelling the role of Sildenafil and SB204741 in suppressing fibrotic potential of peritoneal fibroblasts obtained from PD patients

Chaturvedi,

Singh,

Agarwal

et al. 2024

Front. Pharmacol.

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Introduction: Peritoneal fibrosis (PF) results in technique failure in peritoneal dialysis (PD) patients. Peritoneal fibroblasts are characterized by increase in the ACTA2 gene, responsible for alpha smooth muscle actin (α−SΜΑ), extracellular matrix (ECM) production, and inflammatory cytokines production, which are the are key mediators in the pathogenesis of PF. 5-hydroxytryptamine (5-HT; serotonin) induces ECM synthesis in fibroblasts in a transforming growth factor-beta 1 (TGF-β1) dependent manner. The purpose of our study was to identify the potential mechanism and role of sildenafil and 5HT2B receptor inhibitor (SB204741) combination in attenuating PD-associated peritoneal fibrosis.Methods: Studies were performed to determine the effect of TGF-β1, sildenafil, and SB204741 on human peritoneal fibroblasts (HPFBs) isolated from the parietal peritoneum of patients in long-term PD patients (n = 6) and controls (n = 6). HPFBs were incubated with TGF-β1 (10 ng/mL) for 1 h and later with TGF-β1 (10 ng/mL)/[sildenafil (10 µM) or SB204741 (1 µM)] and their combination for 24 h (post-treatment strategy). In the pre-treatment strategy, HPFBs were pre-treated with sildenafil (10 µM) or SB204741 (1 µM) and a combination of the two for 1 h and later with only TGF-β1 (10 ng/mL) for 24 h.Results: The anti-fibrotic effects of the combination of sildenafil and SB204741 were greater than that of each drug alone. In TGF-β1-stimulated HPFBs, pro-fibrotic genes (COL1A1, COL1A2, ACTA2, CTGF, FN1, and TGFB1) exhibited higher expression than in controls, which are crucial targets of sildenafil and SB204741 against peritoneal fibrosis. The synergistic approach played an anti-fibrotic role by regulating the pro- and anti-fibrotic gene responses as well as inflammatory cytokine responses. The combination treatment significantly attenuated peritoneal fibrosis, as evident by the almost complete amelioration of ACTA2 expression, restoration of anti-fibrotic genes (MMP2/TIMP1), and, at least, by reducing the expression of pro-inflammatory cytokines (IFN-γ, IL-4, IL-17, IL-1β, IL-6, TNF-α, and TGF-β1) along with an increase in IL-10 levels.Discussion: Taken together, the above research evidences that the combination of sildenafil and SB204741 may have therapeutic potential in suppressing peritoneal fibrosis due to peritoneal dialysis.

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Advances in stem cell therapy for peritoneal fibrosis: from mechanisms to therapeutics

Cited by 2 publications

References 131 publications

Coupling Osmotic Efficacy with Biocompatibility in Peritoneal Dialysis: A Stiff Challenge

Coupling Osmotic Efficacy with Biocompatibility in Peritoneal Dialysis: A Stiff Challenge

Unravelling the role of Sildenafil and SB204741 in suppressing fibrotic potential of peritoneal fibroblasts obtained from PD patients

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