The Selection of Peritoneal Mesothelial Cells Is Important for Cell Therapy to Prevent Peritoneal Fibrosis

The Selection of Peritoneal Mesothelial Cells Is Important for Cell Therapy to Prevent Peritoneal Fibrosis
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DOI:
10.1089/ten.tea.2013.0130
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发表时间:
2014-02-01
影响因子:
4.1
通讯作者:
Makino, Hirofumi
Makino, Hirofumi
中科院分区:
医学3区
文献类型:
--
作者:
Kitamura, Shinji;Horimoto, Naoya;Makino, Hirofumi

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长期腹膜透析(PD)导致慢性腹膜损伤。腹膜间皮细胞(PMCs)在腹膜功能中起重要作用。我们研究了使用pmc细胞治疗预防PD患者腹膜损伤的可能性。我们从PD患者的PD排出物中收集人类pmc。根据形态学特征,采用极限稀释法将PMCs分离为上皮样细胞(Epi)和成纤维细胞样细胞(Fib)。我们将这些细胞移植到裸鼠腹膜壁层和内脏层,并用机械刮擦法刮伤。在腹膜壁层和腹膜内脏处检测到移植细胞。与阳性对照组相比,Epi细胞治疗组很少出现粘连,未出现腹膜壁层和内脏层增厚。而Fib细胞治疗组不能抑制腹膜粘连和增厚。移植的Epi细胞表达肝细胞生长因子,而Fib细胞不表达肝细胞生长因子。Fib细胞对血管内皮生长因子的表达强于Epi细胞。同一患者的两种细胞在细胞治疗中表现出不同的特点和效果。这些结果表明,PD患者的PMCs具有Epi细胞和Fib细胞等不同的特征,PMCs的选择对细胞治疗具有重要意义,不仅从细胞直接相互作用的角度考虑,而且从移植细胞分泌细胞因子的角度考虑。此外,细胞形态特征的差异可能影响它们在腹膜再生中的作用。
Long-term peritoneal dialysis (PD) causes chronic peritoneal damage. Peritoneal mesothelial cells (PMCs) play an important role in peritoneal function. We investigated the possibility of cell therapy using the PMCs to prevent peritoneal damage in PD patients. We harvested human PMCs from the PD effluent of PD patients. The PMCs were separated based on morphological characteristics into epithelial-like (Epi) cells and fibroblast-like (Fib) cells by the limiting dilution method. We transplanted these cells into nude mice whose parietal and visceral peritoneum were scratched by mechanical scraping. The transplanted cells were detected at the parietal and visceral peritoneum. Compared with the positive control, the Epi cell therapy group showed very few adhesions and exhibited no thickening of the parietal and visceral peritoneum. However, the group with Fib cell therapy could not inhibit peritoneal adhesion and thickening. In addition, hepatocyte growth factor was expressed by the grafted Epi cells but not Fib cells. Fib cells expressed vascular endothelial growth factor stronger than Epi cells. These two types of cells from the same patient showed different characteristics and effects for cell therapy. These findings suggest that the PMCs from the PD patient showed different characteristics, such as Epi cells and Fib cells, and the selection of PMCs is important for cell therapy on the point of not only the direct cellular interactions but also cytokine secretion from the grafted cells. Furthermore, the differences in the morphological cell characteristics may influence their role in peritoneal regeneration.