Biochemical and biophysical research communications · 2025
Single-cell transcriptomic analysis of interactions of peritoneal mesenchymal stem cells with macrophages in prevention of peritoneal membrane injury.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Lu Jingyuan, Chen Nianzhen, Zong Ming, Xu Zhen, Zhao Xinhui, Xi Minhui, Guan Qiunong, Du Caigan, Fan Lieying, Qi Hualin
Аннотация
AIM: Long-time peritoneal dialysis (PD) causes peritoneal membrane (PM) injury resulting in ultrafiltration failure, for which there is no therapy available. Treatment with peritoneal mesenchymal stem cells (pMSCs) has been demonstrated to prevent PD-induced PM injury. This study was designed to investigate the interactions of pMSCs with macrophages in the prevention of PD-induced PM injury.
METHODS: Sprague-Dawley rats were intraperitoneally exposed to Dianeal solution (PDS, 4.25 % dextrose, 10 mL/rat/day) and treated with pMSCs (2 × 106/rat/wk). The parietal PM injury was determined by histology. Single-cell RNA sequencing was performed using a HiSeq × 10 platform and analyzed using Cell Range software and "Mouse_ref_Immgen" datasets. The macrophage phenotype was determined using STRING databases and flow cytometric assay.
RESULTS: pMSCs treatment significantly reduced the PM thickness and neoangiogenesis induced by exposure to PDS. Single-cell RNA sequencing showed that the PM protection of pMSCs was associated with prevention of fibroblast loss and suppression of vascular endothelium expansion within the submesothelial stroma, where it predominantly increased the population of macrophages among leukocytes tested. Co-culture with pMSC conditioned medium stimulated CD54 expression and proliferation of activated THP-1 monocytes. STRING databases predicted that the regulation of macrophages by pMSCs in PM injury was done by activation of "anti-inflammatory" macrophage subpopulations (Macro1, Macro2, Macro4, and Macro6) and suppression of "cytotoxic" macrophage subpopulations (Macro3 and Macro5).
CONCLUSION: Our data suggest that therapeutic outcome of pMSCs treatment in the prevention of PM injury is possibly mediated by simultaneously suppressing "cytotoxic" macrophages and promoting "anti-inflammatory" macrophages, resulting in protection of PM structure and function.
METHODS: Sprague-Dawley rats were intraperitoneally exposed to Dianeal solution (PDS, 4.25 % dextrose, 10 mL/rat/day) and treated with pMSCs (2 × 106/rat/wk). The parietal PM injury was determined by histology. Single-cell RNA sequencing was performed using a HiSeq × 10 platform and analyzed using Cell Range software and "Mouse_ref_Immgen" datasets. The macrophage phenotype was determined using STRING databases and flow cytometric assay.
RESULTS: pMSCs treatment significantly reduced the PM thickness and neoangiogenesis induced by exposure to PDS. Single-cell RNA sequencing showed that the PM protection of pMSCs was associated with prevention of fibroblast loss and suppression of vascular endothelium expansion within the submesothelial stroma, where it predominantly increased the population of macrophages among leukocytes tested. Co-culture with pMSC conditioned medium stimulated CD54 expression and proliferation of activated THP-1 monocytes. STRING databases predicted that the regulation of macrophages by pMSCs in PM injury was done by activation of "anti-inflammatory" macrophage subpopulations (Macro1, Macro2, Macro4, and Macro6) and suppression of "cytotoxic" macrophage subpopulations (Macro3 and Macro5).
CONCLUSION: Our data suggest that therapeutic outcome of pMSCs treatment in the prevention of PM injury is possibly mediated by simultaneously suppressing "cytotoxic" macrophages and promoting "anti-inflammatory" macrophages, resulting in protection of PM structure and function.