Mitochondrial transplantation: new challenges for cancer

O. I. Kit, E. Frantsiyants, A. Shikhlyarova, I. V. Neskubina
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Abstract

This review discusses the uniqueness of mitochondria providing normal cellular functions and at the same time involved in many pathological conditions, and also analyzes the scientific literature to clarify the effectiveness of mitochondrial transplantation in cancer treatment. Being important and semi-autonomous organelles in cells, they are able to adapt their functions to the needs of the corresponding organ. The ability of mitochondria to reprogram is important for all cell types that can switch between resting and proliferation. At the same time, tumor mitochondria undergo adaptive changes to accelerate the reproduction of tumor cells in an acidic and hypoxic microenvironment. According to emerging data, mitochondria can go beyond the boundaries of cells and move between the cells of the body. Intercellular transfer of mitochondria occurs naturally in humans as a normal mechanism for repairing damaged cells. The revealed physiological mitochondrial transfer has become the basis for a modern form of mitochondrial transplantation, including autologous (isogenic), allogeneic, and even xenogenic transplantation. Currently, exogenous healthy mitochondria are used in treatment of several carcinomas, including breast cancer, pancreatic cancer, and glioma. Investigation of the functional activity of healthy mitochondria demonstrated and confirmed the fact that female mitochondria are more efficient in suppressing tumor cell proliferation than male mitochondria. However, tissue-specific sex differences in mitochondrial morphology and oxidative capacity were described, and few studies showed functional sex differences in mitochondria during therapy. The reviewed studies report that mitochondrial transplantation can be specifically targeted to a tumor, providing evidence for changes in tumor function after mitochondrial administration. Thus, the appearance of the most interesting data on the unique functions of mitochondria indicates the obvious need for mitochondrial transplantation.
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线粒体移植:癌症的新挑战
这篇综述讨论了线粒体在提供正常细胞功能的同时也参与多种病理状况的独特性,并分析了科学文献,以阐明线粒体移植在癌症治疗中的有效性。线粒体是细胞中重要的半自主细胞器,能够根据相应器官的需要调整自身功能。线粒体的重编程能力对所有可在静息和增殖之间切换的细胞类型都很重要。与此同时,肿瘤线粒体也会发生适应性变化,以加速肿瘤细胞在酸性和缺氧微环境中的繁殖。根据新出现的数据,线粒体可以超越细胞的界限,在人体细胞之间移动。线粒体的细胞间转移在人体中自然发生,是修复受损细胞的正常机制。所揭示的线粒体生理性转移已成为现代线粒体移植的基础,包括自体(同种异体)、异种异体甚至异种移植。目前,外源性健康线粒体被用于治疗多种癌症,包括乳腺癌、胰腺癌和胶质瘤。对健康线粒体功能活性的研究表明并证实,雌性线粒体在抑制肿瘤细胞增殖方面比雄性线粒体更有效。不过,线粒体形态和氧化能力方面存在组织特异性别的性别差异,很少有研究显示线粒体在治疗过程中存在功能性性别差异。综述的研究报告指出,线粒体移植可以特异性地靶向肿瘤,为线粒体给药后肿瘤功能的变化提供了证据。因此,关于线粒体独特功能的最有趣数据的出现表明,线粒体移植具有明显的必要性。
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