Tyumen State Medical University, Tyumen, Russian Federation.
Department of Pharmacology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
Stem Cell Res Ther. 2021 Mar 18;12(1):192. doi: 10.1186/s13287-021-02265-1.
Over recent years, mesenchymal stem/stromal cells (MSCs) and their potential biomedical applications have received much attention from the global scientific community in an increasing manner. Firstly, MSCs were successfully isolated from human bone marrow (BM), but in the next steps, they were also extracted from other sources, mostly from the umbilical cord (UC) and adipose tissue (AT). The International Society for Cellular Therapy (ISCT) has suggested minimum criteria to identify and characterize MSCs as follows: plastic adherence, surface expression of CD73, D90, CD105 in the lack of expression of CD14, CD34, CD45, and human leucocyte antigen-DR (HLA-DR), and also the capability to differentiate to multiple cell types including adipocyte, chondrocyte, or osteoblast in vitro depends on culture conditions. However, these distinct properties, including self-renewability, multipotency, and easy accessibility are just one side of the coin; another side is their huge secretome which is comprised of hundreds of mediators, cytokines, and signaling molecules and can effectively modulate the inflammatory responses and control the infiltration process that finally leads to a regulated tissue repair/healing or regeneration process. MSC-mediated immunomodulation is a direct result of a harmonic synergy of MSC-released signaling molecules (i.e., mediators, cytokines, and chemokines), the reaction of immune cells and other target cells to those molecules, and also feedback in the MSC-molecule-target cell axis. These features make MSCs a respectable and eligible therapeutic candidate to be evaluated in immune-mediated disorders, such as graft versus host diseases (GVHD), multiple sclerosis (MS), Crohn's disease (CD), and osteoarthritis (OA), and even in immune-dysregulating infectious diseases such as the novel coronavirus disease 2019 (COVID-19). This paper discussed the therapeutic applications of MSC secretome and its biomedical aspects related to immune-mediated conditions. Sources for MSC extraction, their migration and homing properties, therapeutic molecules released by MSCs, and the pathways and molecular mechanisms possibly involved in the exceptional immunoregulatory competence of MSCs were discussed. Besides, the novel discoveries and recent findings on immunomodulatory plasticity of MSCs, clinical applications, and the methods required for their use as an effective therapeutic option in patients with immune-mediated/immune-dysregulating diseases were highlighted.
近年来，间充质干细胞（MSCs）及其潜在的生物医学应用引起了全球科学界越来越多的关注。首先，MSC 已成功从人骨髓（BM）中分离出来，但在接下来的步骤中，它们也从其他来源中提取出来，主要来自脐带（UC）和脂肪组织（AT）。国际细胞治疗学会（ISCT）提出了识别和表征 MSC 的最低标准，如下所示：塑料粘附、CD73、D90、CD105 的表面表达，在缺乏 CD14、CD34、CD45 和人类白细胞抗原-DR（HLA-DR）的表达，以及在体外分化为多种细胞类型的能力，包括脂肪细胞、软骨细胞或成骨细胞，这取决于培养条件。然而，这些独特的特性，包括自我更新能力、多能性和易于获得性，只是硬币的一面；另一面是它们庞大的分泌组，由数百种介质、细胞因子和信号分子组成，可以有效地调节炎症反应并控制最终导致受调控的组织修复/再生过程的浸润过程。MSC 介导的免疫调节是 MSC 释放的信号分子（即介质、细胞因子和趋化因子）的和谐协同作用、免疫细胞和其他靶细胞对这些分子的反应以及 MSC-分子-靶细胞轴的反馈的直接结果。这些特性使 MSC 成为一种值得尊敬和合格的治疗候选物，可以在免疫介导的疾病中进行评估，例如移植物抗宿主病（GVHD）、多发性硬化症（MS）、克罗恩病（CD）和骨关节炎（OA），甚至在免疫失调感染性疾病中，如 2019 年新型冠状病毒病（COVID-19）。本文讨论了 MSC 分泌组的治疗应用及其与免疫介导条件相关的生物医学方面。讨论了 MSC 提取的来源、它们的迁移和归巢特性、MSC 释放的治疗分子以及可能涉及 MSC 异常免疫调节能力的途径和分子机制。此外，还强调了 MSC 免疫调节可塑性的新发现和最近发现、临床应用以及将其用作免疫介导/免疫失调疾病患者有效治疗选择的方法。
