大鼠脂肪组织源性干细胞减轻酵母聚糖诱导的腹膜炎大鼠腹膜损伤并伴有补体激活。
Rat adipose tissue-derived stem cells attenuate peritoneal injuries in rat zymosan-induced peritonitis accompanied by complement activation.
机构信息
Division of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Division of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Renal Replacement Therapy, Nagoya University Graduate School of Medicine, Nagoya, Japan.
出版信息
Cytotherapy. 2014 Mar;16(3):357-68. doi: 10.1016/j.jcyt.2013.10.011. Epub 2013 Dec 22.
BACKGROUND AIMS
In patients receiving peritoneal dialysis, fungal or yeast peritonitis has a poor prognosis. In rat peritoneum with mechanical scraping, severe peritonitis can be induced by zymosan, a component of yeast (Zy/scraping peritonitis). Administration of rat adipose tissue-derived stromal cells (ASCs) potentially can improve several tissue injuries. The present study investigated whether rat ASCs could improve peritoneal inflammation in Zy/scraping peritonitis.
METHODS
Rat ASCs were injected intraperitoneally on a daily basis in rats with Zy/scraping peritonitis.
RESULTS
Peritoneal inflammation accompanied by accumulation of inflammatory cells and complement deposition was suppressed by day 5 after injection of rat ASCs. The peritoneal mesothelial layer in Zy/scraping peritonitis with rat ASC treatment was restored compared with the peritoneal mesothelial layer without rat ASC treatment. Injected rat ASCs co-existed with mesothelial cells in the sub-peritoneal layer. In vitro assays showed increased cellular proliferation of rat mesothelial cells combined with rat ASCs by co-culture assays, confirming that fluid factors from rat ASCs might play some role in facilitating the recovery of rat mesothelial cells. Hepatocyte growth factor was released from rat ASCs, and administration of recombinant hepatocyte growth factor increased rat mesothelial cell proliferation.
CONCLUSIONS
Because the peritoneal mesothelium shows strong expression of membrane complement regulators such as Crry, CD55 and CD59, restoration of the mesothelial cell layer by rat ASCs might prevent deposition of complement activation products and ameliorate peritoneal injuries. This study suggests the therapeutic possibilities of intraperitoneal rat ASC injection to suppress peritoneal inflammation by restoring the mesothelial layer and decreasing complement activation in fungal or yeast peritonitis.
背景目的
在接受腹膜透析的患者中，真菌或酵母性腹膜炎预后不良。在大鼠腹膜机械刮除模型中，酵母的一种成分（酵母聚糖/刮除腹膜炎）可诱导严重的腹膜炎。脂肪组织来源的基质细胞（ASCs）给药可能改善多种组织损伤。本研究探讨了大鼠 ASCs 是否能改善酵母聚糖/刮除腹膜炎中的腹膜炎症。
方法
在酵母聚糖/刮除腹膜炎大鼠中，每日经腹腔内注射大鼠 ASCs。
结果
在注射大鼠 ASCs 后第 5 天，腹膜炎症伴炎症细胞积聚和补体沉积得到抑制。与未接受大鼠 ASC 治疗的大鼠相比，大鼠 ASC 治疗后的腹膜间皮层得到恢复。注射的大鼠 ASC 与亚腹膜层中的间皮细胞共存。体外实验显示，大鼠间皮细胞与大鼠 ASC 共培养后细胞增殖增加，证实大鼠 ASC 分泌的细胞因子可能在促进大鼠间皮细胞恢复中发挥一定作用。大鼠 ASCs 释放肝细胞生长因子，给予重组肝细胞生长因子可增加大鼠间皮细胞增殖。
结论
由于腹膜间皮细胞强烈表达膜补体调节蛋白，如 Crry、CD55 和 CD59，大鼠 ASCs 恢复间皮细胞层可能防止补体激活产物的沉积，并改善腹膜损伤。本研究提示腹腔内注射大鼠 ASC 可能通过恢复间皮层和减少真菌或酵母性腹膜炎中的补体激活来抑制腹膜炎症。
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