Exploring the potential of in vitro extracellular vesicle generation in reproductive biology

Roksan Franko, Marcia de Almeida Monteiro Melo Ferraz
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Abstract

The interest in the growing field of extracellular vesicle (EV) research highlights their significance in intercellular signalling and the selective transfer of biological information between donor and recipient cells. EV studies have provided valuable insights into intercellular communication mechanisms, signal identification and their involvement in disease states, offering potential avenues for manipulating pathological conditions, detecting biomarkers and developing drug-delivery systems. While our understanding of EV functions in reproductive tissues has significantly progressed, exploring their potential as biomarkers for infertility, therapeutic interventions and enhancements in assisted reproductive technologies remains to be investigated. This knowledge gap stems partly from the difficulties associated with large-scale EV production relevant to clinical applications. Most existing studies on EV production rely on conventional 2D cell culture systems, characterized by suboptimal EV yields and a failure to replicate in vivo conditions. This results in the generation of EVs that differ from their in vivo counterparts. Hence, this review firstly delves into the importance of EVs in reproduction to then expand on current techniques for in vitro EV production, specifically examining diverse methods of culture and the potential of bioengineering technologies to establish innovative systems for enhanced EV production.

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探索体外细胞外囊泡生成在生殖生物学中的潜力。
细胞外囊泡(EV)研究领域的兴趣日益浓厚,这凸显了它们在细胞间信号传递以及供体细胞和受体细胞之间有选择性地传递生物信息方面的重要作用。EV研究为细胞间通信机制、信号识别及其在疾病状态中的参与提供了宝贵的见解,为控制病理状态、检测生物标记物和开发药物输送系统提供了潜在的途径。虽然我们对 EV 在生殖组织中功能的认识有了长足的进步,但探索其作为不孕症生物标志物、治疗干预和辅助生殖技术改进的潜力仍有待研究。这一知识空白部分源于与临床应用相关的大规模 EV 生产的困难。现有的大多数 EV 生产研究都依赖于传统的二维细胞培养系统,其特点是 EV 产量不理想,而且无法复制体内条件。这导致生成的 EV 与体内对应物不同。因此,本综述首先深入探讨了 EVs 在生殖过程中的重要性,然后扩展了目前的体外 EV 生产技术,特别研究了各种培养方法以及生物工程技术在建立创新系统以提高 EV 生产方面的潜力。
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