Gouveia Priscila Q, Fanelli Camilla, Ornellas Felipe M, Garnica Margoth R, Francini Ana L R, Murata Gilson M, Matheus Luiz H G, Morales Marcelo M, Noronha Irene L
Laboratory of Cellular, Genetic, and Molecular Nephrology, Renal Division, Medical School, University of São Paulo, São Paulo 01246-903, Brazil.
Laboratory of Carbohydrate and Radioimmunoassay, School of Medicine, University of São Paulo, São Paulo 01246-903, Brazil.
Cells. 2025 Mar 14;14(6):436. doi: 10.3390/cells14060436.
Cell therapy utilizing mesenchymal stromal cells (MSCs) through paracrine mechanisms holds promise for regenerative purposes. Peritoneal fibrosis (PF) is a significant complication of peritoneal dialysis. Various strategies have been proposed to protect the peritoneal membrane (PM). This study explores the effectiveness of adipose-tissue-derived stem cells (ASCs) and extracellular vesicles (EVs) at mitigating PF using a rat model of PF induced by chlorhexidine gluconate. ASC and EV treatments effectively prevented an increase in the thickness of the PM and diminished the number of myofibroblasts, fibronectin expression, collagen III expression, and PF-related factors such as TGF-β and FSP-1. Smad3 gene expression decreased in the treatment groups, whereas Smad7 gene expression increased in treated animals. In addition, ASC and EV injections showed potent anti-inflammatory effects. Glucose transport through the PM remained unaffected in relation to the PF group; both treatments promoted an increase in ultrafiltration (UF) capacity. The PF+EVs treated group showed the highest increase in UF capacity. Another critical aspect of ASC and EV treatments was their impact on neoangiogenesis in the PM which is vital for UF capacity. Although the treated groups displayed a significant decrease in VEGF expression in the PM, peritoneal function remained effective. In conclusion, within the experimental PF model, both ASC and EV treatments demonstrated anti-inflammatory effects and comparably hindered the progression of PF. The EV treatment exhibited superior preservation of peritoneal function, along with enhanced UF capacity. These findings suggest the potential of ASCs and EVs as novel therapeutic approaches to prevent the development of PF associated with peritoneal dialysis.
通过旁分泌机制利用间充质基质细胞（MSCs）进行细胞治疗在再生医学领域具有广阔前景。腹膜纤维化（PF）是腹膜透析的一个严重并发症。人们已经提出了各种策略来保护腹膜（PM）。本研究使用葡萄糖酸氯己定诱导的PF大鼠模型，探讨脂肪组织来源的干细胞（ASCs）和细胞外囊泡（EVs）减轻PF的有效性。ASC和EV治疗有效防止了PM厚度增加，并减少了肌成纤维细胞数量、纤连蛋白表达、胶原蛋白III表达以及PF相关因子如TGF-β和FSP-1。治疗组中Smad3基因表达下降，而治疗动物中Smad7基因表达增加。此外，ASC和EV注射显示出强大的抗炎作用。与PF组相比，通过PM的葡萄糖转运未受影响；两种治疗均促进了超滤（UF）能力的增加。PF+EVs治疗组的UF能力增加最高。ASC和EV治疗的另一个关键方面是它们对PM中新生血管形成的影响，这对UF能力至关重要。尽管治疗组PM中VEGF表达显著下降，但腹膜功能仍然有效。总之，在实验性PF模型中，ASC和EV治疗均显示出抗炎作用，并同等程度地阻碍了PF的进展。EV治疗在保留腹膜功能方面表现更优，同时增强了UF能力。这些发现表明ASCs和EVs作为预防腹膜透析相关PF发展的新型治疗方法具有潜力。
