Mesenchymal stem cells (MSCs) play an important role in tissue homeostasis and damage repair through their ability to differentiate into cells of different tissues, trophic support, and immunomodulation. These properties made them attractive for clinical applications in regenerative medicine, immune disorders, and cell transplantation. However, despite multiple preclinical and clinical studies demonstrating beneficial effects of MSCs, their native identity and mechanisms of action remain inconclusive. Since its discovery, the CD73/ecto-5′-nucleotidase is known as a classic marker for MSCs, but its role goes far beyond a phenotypic characterization antigen. CD73 contributes to adenosine production, therefore, is an essential component of purinergic signaling, a pathway composed of different nucleotides and nucleosides, which concentrations are finely regulated by the ectoenzymes and receptors. Thus, purinergic signaling controls pathophysiological functions such as proliferation, migration, cell fate, and immune responses. Despite the remarkable progress already achieved in considering adenosinergic pathway as a therapeutic target in different pathologies, its role is not fully explored in the context of the therapeutic functions of MSCs. Therefore, in this review, we provide an overview of the role of CD73 and adenosine-mediated signaling in the functions ascribed to MSCs, such as homing and proliferation, cell differentiation, and immunomodulation. Additionally, we will discuss the pathophysiological role of MSCs, via CD73 and adenosine, in different diseases, as well as in tumor development and progression. A better understanding of the adenosinergic pathway in the regulation of MSCs functions will help to provide improved therapeutic strategies applicable in regenerative medicine.

中文翻译：

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间充质干细胞命运和功能中的腺苷能通路

间充质干细胞 (MSCs) 通过分化为不同组织细胞的能力、营养支持和免疫调节在组织稳态和损伤修复中发挥重要作用。这些特性使它们对再生医学、免疫疾病和细胞移植的临床应用具有吸引力。然而，尽管多项临床前和临床研究证明了 MSC 的有益作用，但它们的天然特性和作用机制仍然没有定论。自发现以来，CD73/ecto-5'-核苷酸酶被称为 MSC 的经典标志物，但其作用远远超出了表型表征抗原。CD73 有助于产生腺苷，因此，它是嘌呤能信号传导的重要组成部分，这是一种由不同核苷酸和核苷组成的途径，其浓度由胞外酶和受体精细调节。因此，嘌呤能信号控制病理生理功能，如增殖、迁移、细胞命运和免疫反应。尽管在将腺苷能通路作为不同病理的治疗靶点方面已经取得了显着进展，但在 MSCs 的治疗功能背景下，其作用尚未得到充分探索。因此，在这篇综述中，我们概述了 CD73 和腺苷介导的信号传导在归因于 MSCs 的功能中的作用，例如归巢和增殖、细胞分化和免疫调节。此外，我们将讨论 MSC 通过 CD73 和腺苷在不同疾病以及肿瘤发展和进展中的病理生理作用。