研究动态
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间质干细胞对细胞-细胞接触抑制所产生的自分泌因子具有抗肿瘤性质。

Autocrine Factors Produced by Mesenchymal Stem Cells in Response to Cell-Cell Contact Inhibition Have Anti-Tumor Properties.

发表日期:2023 Aug 26
作者: Jerry P Chen, Rong Li, Jean X Jiang, Xiao-Dong Chen
来源: Stem Cell Research & Therapy

摘要:

近年来,间充质干细胞(MSC)疗法受到质疑,因为MSC既能促进肿瘤发生,也能抑制肿瘤发生。MSC和肿瘤细胞都能通过复制来增加其种群规模;然而,当达到密度抑制时,MSC停止细胞分裂并进行分化,而肿瘤细胞却不会。我们假设密度抑制会导致密集生长的MSC产生效应物质,而这些效应物质可以抑制肿瘤细胞的生长。为了验证这一假设,我们分别将乳腺癌细胞(MDA-MB-231)与达到密度抑制或亚密度抑制的骨髓源性MSC(BM-MSCs)共培养,并将各种肿瘤细胞用密度抑制或亚密度抑制的BM-MSCs获得的条件培养基(CM)处理。结果显示,与亚密度抑制的BM-MSCs共培养或用亚密度抑制的BM-MSCs获得的CM处理的肿瘤细胞相比,与达到密度抑制的BM-MSCs共培养或用达到密度抑制的BM-MSCs获得的CM处理的肿瘤细胞的生长受到了抑制,并且这个效果显著强于前者。通过携带CM接种肿瘤细胞可以完全阻止皮下肿瘤形成。未来,通过密度抑制的MSC产生的可溶性抗肿瘤效应物质可能被用作无细胞疗法;这种方法提供了解决与细胞疗法相关问题的方案。
Recently, mesenchymal stem cell (MSC) therapies have been questioned as MSCs are capable of both promoting and inhibiting tumorigenesis. Both MSCs and tumor cells replicate to increase their population size; however, MSCs, but not tumor cells, stop dividing when they reach confluence due to cell-cell contact inhibition and then differentiate. We hypothesized that contact inhibition results in the production of effector molecules by confluent MSCs and these effectors are capable of suppressing tumor cell growth. To test this hypothesis, we co-cultured breast cancer cells (MDA-MB-231) with either confluent or sub-confluent bone-marrow-derived MSCs (BM-MSCs); in addition, we treated various tumor cells with conditioned media (CM) obtained from either confluent or sub-confluent BM-MSCs. The results showed that the growth of tumor cells co-cultured with confluent BM-MSCs or treated with CM obtained from confluent BM-MSCs was inhibited, and this effect was significantly stronger than that seen with tumor cells co-cultured with sub-confluent BM-MSCs or CM obtained from sub-confluent BM-MSCs. Subcutaneous tumor formation was completely prevented by the inoculation of tumor cells mixed with CM. In the future, soluble anti-tumor effectors, produced by confluent MSCs, may be used as cell-free therapeutics; this approach provides a solution to current concerns associated with cell-based therapies.