Cargnoni Anna, Gibelli Lucia, Tosini Alessandra, Signoroni Patrizia Bonassi, Nassuato Claudia, Arienti Davide, Lombardi Guerino, Albertini Alberto, Wengler Georg S, Parolini Ornella
Centro di Ricerca E. Menni, Fondazione Poliambulanza-Istituto Ospedaliero, 25124 Brescia, Italy.
Cell Transplant. 2009;18(4):405-22. doi: 10.3727/096368909788809857.
Fetal membranes (amnion and chorion) have recently raised significant attention as potential sources of stem cells. We have recently demonstrated that cells derived from human term placenta show stem cell phenotype, high plasticity, and display low immunogenicity both in vitro and in vivo. Moreover, placenta-derived cells, after xenotransplantation, are able to engraft in solid organs including the lung. On these bases, we studied the effects of fetal membrane-derived cells on a mouse model of bleomycin-induced lung fibrosis. Fetal membrane-derived cells were infused 15 min after intratracheal bleomycin instillation. Different delivery routes were used: intraperitoneal or intratracheal for both xenogeneic and allogeneic cells, and intravenous for allogeneic cells. The effects of the transplanted cells on bleomycin-induced inflammatory and fibrotic processes were then scored and compared between transplanted and control animals at different time points. By PCR and immunohistochemistry analyses, we demonstrated the presence of transplanted cells 3, 7, 9, and 14 days after transplantation. Concomitantly, we observed a clear decrease in neutrophil infiltration and a significant reduction in the severity of bleomycin-induced lung fibrosis in mice treated with placenta-derived cells, irrespective of the source (allogeneic or xenogeneic) or delivery route. Our findings constitute further evidence in support of the hypothesis that placenta-derived cells could be useful for clinical application, and warrant further studies toward the use of these cells for the repair of tissue damage associated with inflammatory and fibrotic degeneration.
胎膜（羊膜和绒毛膜）作为干细胞的潜在来源最近引起了极大关注。我们最近证明，源自人类足月胎盘的细胞在体外和体内均表现出干细胞表型、高可塑性且免疫原性低。此外，胎盘来源的细胞在异种移植后能够在包括肺在内的实体器官中植入。基于这些，我们研究了胎膜来源的细胞对博来霉素诱导的小鼠肺纤维化模型的影响。在气管内注入博来霉素15分钟后注入胎膜来源的细胞。使用了不同的给药途径：异种和同种异体细胞均采用腹腔内或气管内给药，同种异体细胞采用静脉内给药。然后在不同时间点对移植细胞对博来霉素诱导的炎症和纤维化过程的影响进行评分，并在移植动物和对照动物之间进行比较。通过PCR和免疫组织化学分析，我们证明了移植后3、7、9和14天存在移植细胞。同时，我们观察到在用胎盘来源的细胞治疗的小鼠中，中性粒细胞浸润明显减少，博来霉素诱导的肺纤维化严重程度显著降低，无论来源（同种异体或异种）或给药途径如何。我们的研究结果进一步证明了胎盘来源的细胞可用于临床应用这一假设，并为进一步研究使用这些细胞修复与炎症和纤维化变性相关的组织损伤提供了依据。
