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首页> 外文期刊>Tissue engineering, Part A >Regenerative therapy and cancer: in vitro and in vivo studies of the interaction between adipose-derived stem cells and breast cancer cells from clinical isolates.
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Regenerative therapy and cancer: in vitro and in vivo studies of the interaction between adipose-derived stem cells and breast cancer cells from clinical isolates.

机译:再生疗法和癌症:来自临床分离株的脂肪干细胞与乳腺癌细胞之间相互作用的体外和体内研究。

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Adipose-derived stem cells (ASCs) have been proposed to stabilize autologous fat grafts for regenerative therapy, but their safety is unknown in the setting of reconstructive surgery after mastectomy. Both bone marrow mesenchymal stem cells (MSCs) and ASC have been shown to enhance tumorigenesis of established breast cancer cell lines, but primary patient material has not been tested. Here, we ask whether ASC promote the in vitro growth and in vivo tumorigenesis of metastatic breast cancer clinical isolates. Metastatic pleural effusion (MPE) cells were used for coculture experiments. ASC enhanced the proliferation of MPE cells in vitro (5.1-fold). For xenograft experiments (100 sorted cells/injection site), nonhematopoietic MPE cells were sorted into resting and active populations: CD90+ resting (low scatter, 2.1%>/=2N DNA), CD90+ active (high scatter, 10.6%>/=2N DNA), and CD90-. Resting CD90+ MPE cells were tumorigenic in 4/40 sites but growth was not augmented by ASC. Active CD90+ MPE cells were tumorigenic (17/40 sites) only when coinjected with ASC (p=0.0005, chi2 test). The multilineage potentiality and MSC-like immunophenotype of ASC were confirmed by flow cytometry, differentiation cultures, and immunostaining. The secretome profile of ASC resembled that reported for MSC, but included adipose-associated adipsin and the hormone leptin, shown to promote breast cancer growth. Our data indicate that ASC enhance the growth of active, but not resting tumor cells. Thus, reconstructive therapy utilizing ASC-augmented whole fat should be postponed until there is no evidence of active disease.
机译:已经提出了脂肪来源的干细胞(ASC)来稳定自体脂肪移植物的再生治疗,但是在乳房切除术后的重建手术中,其安全性尚不清楚。骨髓间充质干细胞(MSCs)和ASC均能增强已建立的乳腺癌细胞系的肿瘤发生能力,但尚未测试主要的患者材料。在这里,我们问ASC是否促进转移性乳腺癌临床分离株的体外生长和体内肿瘤发生。转移性胸腔积液(MPE)细胞用于共培养实验。 ASC增强了MPE细胞的体外增殖(5.1倍)。对于异种移植实验(100个分选的细胞/注射位点),将非造血性MPE细胞分为静息和活跃群体:CD90 +静息(低散点,2.1%/ = 2N DNA),CD90 +活跃(高散点,10.6%> / = 2N) DNA)和CD90-。静止的CD90 + MPE细胞在4/40个位点具有致瘤性,但ASC不能促进其生长。仅当与ASC共注射时,活性CD90 + MPE细胞才具有致瘤性(17/40个位点)(p = 0.0005,chi2测试)。流式细胞仪,分化培养和免疫染色证实了ASC的多谱系潜能和类MSC免疫表型。 ASC的分泌组图谱与MSC报道的相似,但包括与脂肪相关的脂肪蛋白和荷尔蒙瘦素,它们可促进乳腺癌的生长。我们的数据表明,ASC增强了活跃的肿瘤细胞的生长,但没有增强。因此,应该推迟利用ASC增添的全脂进行的重建治疗,直到没有活动性疾病的证据为止。

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