肿瘤细胞治疗研究
英文原题：Cancer cell-dependent increase in senescence-like populations following exosome treatment from bone marrow and induced pluripotent stem cell-derived mesenchymal stem cells.
iMSC-Exos 通过类衰老机制有效抑制肿瘤增殖和侵袭。这些结果表明，iMSC-Exos 可作为无细胞癌症疗法，值得进一步在动物模型中进行评估。
间充质干细胞（MSC）细胞外囊泡，尤其是外泌体（Exos），因其能够调节肿瘤细胞生物学特性，正日益被视为有前景的癌症治疗工具。诱导多能干细胞来源的MSC（iMSC）因其增殖能力和增强的分化潜能，与常规MSC相比显示出治疗特性。
研究iMSCs来源的外泌体（iMSC-Exos）和骨髓MSCs来源的外泌体（BMSC-Exos）对PANC1和MDA-MB-231癌细胞的影响。
iMSCs 和 BMSCs 根据国际细胞治疗学会（2006）标准，通过验证 MSC 特异性标志物的表达及其分化潜能进行表征。Exos 采用序贯超速离心法从 48 小时条件培养基中分离，并基于大小、形态以及包括 CD9、CD81 和 CD63 在内的表面标志物表达进行表征。用分离的 Exos 处理 PANC1 和 MDA-MB-231 细胞，并评估其对细胞增殖、凋亡、衰老和侵袭的影响。
在PANC1细胞中，iMSC-Exos维持抗增殖活性达48小时（减少35%，P < 0.01），而BMSC-Exos仅有一过性作用。在MDA-MB-231细胞中，两种Exos在48小时后均显著降低增殖（分别减少约28%和约22%，P < 0.05）。值得注意的是，这些抗增殖效应与凋亡无关，但衰老样肿瘤细胞增加被确定为主要反应，在两种癌细胞系中，iMSC-Exos诱导的衰老相关-半乳糖苷酶阳性细胞数量比BMSC-Exos高约2.3倍。在PANC1和MDA-MB-231细胞中，iMSC-Exos显著抑制肿瘤细胞侵袭（分别减少约60%和约45%，P < 0.001），而BMSC-Exos仅在PANC1细胞中抑制侵袭。
BACKGROUND: Mesenchymal stem cell (MSC) extracellular vesicles, particularly exosomes (Exos), are gaining recognition as promising therapeutic tools for cancer due to their capacity to modulate tumor cell biology. Induced pluripotent stem cell-derived MSCs (iMSCs) revealed therapeutic characteristics compared with conventional MSCs due to their proliferative capacity and enhanced differentiation potential. AIM: To study the impact of Exos derived from iMSCs (iMSC-Exos) and bone marrow MSCs (BMSC-Exos) on PANC1 and MDA-MB-231 cancer cells. METHODS: The iMSCs and BMSCs were characterized based on the International Society for Cellular Therapy (2006) criteria by verifying the expression of MSC-specific markers and their differentiation potential. Exos were isolated from 48-hour conditioned media using sequential ultracentrifugation and characterized based on size, morphology, and expression of surface markers including CD9, CD81, and CD63. PANC1 and MDA-MB-231 cells were treated with the isolated Exos, and their effects on cell proliferation, apoptosis, senescence, and invasion were assessed. RESULTS: In PANC1 cells iMSC-Exos sustained antiproliferative activity for 48 hours (35% reduction, P < 0.01) while BMSC-Exos had a transient effect. In MDA-MB-231 cells, both Exos lowered proliferation significantly after 48 hours (~28% and ~22% reduction, P < 0.05). Notably, these antiproliferative effects were not associated with apoptosis, but an increase in senescence-like tumor cells was identified as the primary response with iMSC-Exos inducing approximately 2.3-fold higher number of senescence-associated -galactosidase-positive cells compared with BMSC-Exos across both cancer cell lines. Tumor cell invasion was markedly inhibited in PANC1 and MDA-MB-231 cells in response to iMSC-Exos (~60% and ~45% reduction, respectively, P < 0.001), and only in PANC1 cells in response to BMSC-Exos. CONCLUSION: iMSC-Exos effectively inhibited tumor proliferation and invasion via a senescence-like mechanism. These results indicated that iMSC-Exos could serve as a cell-free cancer therapy and merit further animal model evaluation.
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