Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Autonomous University of Nuevo Leon, Monterrey, Nuevo León 64460, Mexico.
Laboratory of Molecular Genetics, Department of Basic Sciences, University of Monterrey, Monterrey, Nuevo León 66238, Mexico.
Mol Med Rep. 2022 Jun;25(6). doi: 10.3892/mmr.2022.12722. Epub 2022 Apr 29.
As the understanding of cancer grows, new therapies have been proposed to improve the well-known limitations of current therapies, whose efficiency relies mostly on early detection, surgery and chemotherapy. Mesenchymal stem cells (MSCs) have been introduced as a promissory and effective therapy. This fact is due to several useful features of MSCs, such as their accessibility and easy culture and expansion , and their remarkable ability for 'homing' towards tumors, allowing MSCs to exert their anticancer effects directly into tumors. Additionally, MSCs offer the practicability of being genetically engineered to carry anticancer genes, increasing their specificity and efficacy for fighting tumors. In the present study, the antitumoral efficacy and post-implant survival of mice bearing lymphomas implanted intratumorally were determined using mouse bone marrow-derived (BM)-MSCs transduced with soluble TRAIL (sTRAIL), full length TRAIL (flTRAIL), or interferon β (IFNβ), naïve BM-MSCs, or combinations of these. The percentage of surviving mice was determined once all not-implanted mice succumbed. It was found that the percentage of surviving mice implanted with the combination of MSCs-sTRAIL and MSCs-IFN-β was 62.5%. Lymphoma model achieved 100% fatality in the non-treated group by day 41. On the other hand, the percentage of surviving mice implanted with MSCs-sTRAIL was 50% and with MSCs-INFβ 25%. All the aforementioned differences were statistically significant (P<0.05). In conclusion, all implants exhibited tumor size reduction, growth delay, or apparent tumor clearance. MSCs proved to be effective anti-lymphoma agents; additionally, the combination of soluble TRAIL and IFN-β resulted in the most effective antitumor and life enlarging treatment, showing an additive antitumoral effect compared with individual treatments.
随着对癌症认识的不断深入，已经提出了新的治疗方法，以改善当前治疗方法的明显局限性，这些治疗方法的效率主要依赖于早期检测、手术和化疗。间充质干细胞（MSCs）被引入作为一种有前途和有效的治疗方法。这一事实归因于 MSCs 的几个有用特性，例如它们的可及性和易于培养和扩增，以及它们向肿瘤“归巢”的显著能力，使 MSCs 能够直接将其抗癌作用发挥到肿瘤中。此外，MSCs 提供了被基因工程改造以携带抗癌基因的可行性，从而提高了其针对肿瘤的特异性和疗效。在本研究中，通过肿瘤内植入的淋巴肿瘤来确定用转导可溶性 TRAIL（sTRAIL）、全长 TRAIL（flTRAIL）或干扰素β（IFNβ）的骨髓来源的（BM）-MSCs 转染的、未处理的 BM-MSCs 或这些的组合治疗荷瘤小鼠的抗肿瘤功效和植入后存活率。当所有未植入的小鼠死亡时，确定存活小鼠的百分比。结果发现，植入 MSC-sTRAIL 和 MSC-IFN-β 组合的小鼠中，有 62.5%的小鼠存活。在未治疗组中，淋巴肿瘤模型在第 41 天达到 100%的死亡率。另一方面，植入 MSC-sTRAIL 的小鼠中有 50%存活，而植入 MSC-INFβ 的小鼠中有 25%存活。所有上述差异均具有统计学意义（P<0.05）。总之，所有植入物均表现出肿瘤体积缩小、生长延迟或明显的肿瘤清除。MSCs 被证明是有效的抗淋巴肿瘤剂；此外，sTRAIL 和 IFN-β 的组合导致了最有效的抗肿瘤和延长生命的治疗，与单独治疗相比表现出相加的抗肿瘤作用。
