Inhibition of Human Malignant Pleural Mesothelioma Growth by Mesenchymal Stromal Cells.

Inhibition of Human Malignant Pleural Mesothelioma Growth by Mesenchymal Stromal Cells.
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DOI:
10.3390/cells10061427
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发表时间:
2021-06-08
期刊:
影响因子:
6
通讯作者:
Pessina A
Pessina A
中科院分区:
生物学2区
文献类型:
--
作者:
Coccè V;La Monica S;Bonelli M;Alessandri G;Alfieri R;Lagrasta CA;Madeddu D;Frati C;Flammini L;Lisini D;Marcianti A;Parati E;Paino F;Giannì A;Farronato G;Falco A;Spaggiari L;Petrella F;Pessina A

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背景资料:恶性胸膜间皮瘤(MPM)是一种侵袭性肿瘤,其发病率与石棉暴露有关,无有效治疗且预后不良。间充质基质细胞(MSC)在癌症中的作用是有争议的,因为它们对肿瘤生长的相反作用,特别是,只有少数数据报告MSC和MPM。方法:我们研究了脂肪组织来源的MSC,其裂解物和分泌组对不同MPM细胞系的体外功效。在生物反应器中大规模生产MSC后,还在小鼠中的人MPM异种移植物上评价了它们的功效。结果:MSCs、其裂解物和分泌体在体外均能抑制MPM细胞增殖,使细胞周期分别阻滞于S期和G 0/G1期。MSC裂解物通过凋亡诱导细胞死亡。MSC的功效通过显著抑制肿瘤生长在体内得到证实,类似于通过全身施用紫杉醇产生的抑制。有趣的是,在最后一次MSC治疗后没有观察到肿瘤进展,而肿瘤在停止化疗治疗后又开始生长。结论:这些数据第一次证明了MSC通过旁分泌和细胞间相互作用机制诱导了对人间皮瘤生长的显著抑制。由于MPM患者的预后差,并且护理选择仅限于化疗,因此MSC可以为这种恶性肿瘤提供潜在的新治疗方法。
Background: Malignant Pleural Mesothelioma (MPM) is an aggressive tumor that has a significant incidence related to asbestos exposure with no effective therapy and poor prognosis. The role of mesenchymal stromal cells (MSCs) in cancer is controversial due to their opposite effects on tumor growth and in particular, only a few data are reported on MSCs and MPM. Methods: We investigated the in vitro efficacy of adipose tissue-derived MSCs, their lysates and secretome against different MPM cell lines. After large-scale production of MSCs in a bioreactor, their efficacy was also evaluated on a human MPM xenograft in mice. Results: MSCs, their lysate and secretome inhibited MPM cell proliferation in vitro with S or G0/G1 arrest of the cell cycle, respectively. MSC lysate induced cell death by apoptosis. The efficacy of MSC was confirmed in vivo by a significant inhibition of tumor growth, similar to that produced by systemic administration of paclitaxel. Interestingly, no tumor progression was observed after the last MSC treatment, while tumors started to grow again after stopping chemotherapeutic treatment. Conclusions: These data demonstrated for the first time that MSCs, both through paracrine and cell-to-cell interaction mechanisms, induced a significant inhibition of human mesothelioma growth. Since the prognosis for MPM patients is poor and the options of care are limited to chemotherapy, MSCs could provide a potential new therapeutic approach for this malignancy.
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