Abstract
Extracellular vesicles (EVs) are tiny biological nanovesicles ranging from approximately 30–1000 nm in diameter that are released into the extracellular matrix of most cell types and in biofluids. The classification of EVs includes exosomes, microvesicles, and apoptotic bodies, dependent on various factors such as size, markers, and biogenesis pathways. The transition of EV relevance from that of being assumed as a trash bag to be a key player in critical physiological and pathological conditions has been revolutionary in many ways. EVs have been recently revealed to play a crucial role in stem cell biology and cancer progression via intercellular communication, contributing to organ development and the progression of cancer. This review focuses on the significant research progress made so far in the role of the crosstalk between EVs and stem cells and their niche, and cellular communication among different germ layers in developmental biology. In addition, it discusses the role of EVs in cancer progression and their application as therapeutic agents or drug delivery vehicles. All such discoveries have been facilitated by tremendous technological advancements in EV-associated research, especially the microfluidics systems. Their pros and cons in the context of characterization of EVs are also extensively discussed in this review. This review also deliberates the role of EVs in normal cell processes and disease conditions, and their application as a diagnostic and therapeutic tool. Finally, we propose future perspectives for EV-related research in stem cell and cancer biology.
Highlights
Diverse communication systems mediate intercellular communication, both in physiological and pathological conditions, such as cellular junctions, integrins, and selectins (Martin et al, 2013)
This review introduces the biology and historical perspective of Extracellular vesicles (EVs), the role of the crosstalk between EVs produced by stem cells and stem cellsniche, and EV-mediated communication between different germ layers in developmental biology
Components of stem cell-niche and the crosstalk between stem cells and stem cell-niche via EVs. (A) A representative diagram showing proposed stem cell-niche forming a dynamic microenvironment based on constituents reported previously
Summary
Diverse communication systems mediate intercellular communication, both in physiological and pathological conditions, such as cellular junctions (tight junction, adherence junctions, gap junctions, and desmosomes), integrins, and selectins (Martin et al, 2013). Prostate cancer cell (PCa)-derived EVs carry cancer associated fibroblasts (CAF) that play a crucial role in communication between PCa and the tumor microenvironment (TME) to support pathways associated with stemness (Kato et al, 2017). Another study by Deng et al showed that miR155 in exosomes isolated from gastric carcinoma cells caused angiogenesis via targeting of the c-MTB-VEGF pathway in ECs, indicating that miR-155 in EVs can be a potential therapeutic target for gastric carcinoma (Deng et al, 2020). Recent research has demonstrated the functionality of ovarian cancer-derived EVs carrying miR205 that induce angiogenesis via regulation of the PTENAKT pathway in ECs in vitro and in vivo (He et al, 2019). Certain stem cells including MSCs release EVs that facilitates communication in the tumor niche and plays a diverse role in metastasis, angiogenesis, and tumor formation.
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