Table_1_Functional and Immune Modulatory Characteristics of Bone Marrow Mesenchymal Stromal Cells in Patients With Aplastic Anemia: A Systematic Review.docx

BackgroundIn most patients with aplastic anemia (AA), the diagnosis is limited to a description of the symptoms. Lack of understanding of the underlying pathophysiological mechanisms causing bone marrow failure (BMF), hampers tailored treatment. In these patients, auto-immune cell-mediated destruction of the bone marrow is often presumed to be the causative mechanism. The status of the bone marrow microenvironment, particularly the mesenchymal stromal cell (MSC) component, was recently suggested as a potential player in the pathophysiology of AA. Therefore, functional, and immune modulatory characteristics of bone marrow MSCs might represent important parameters for AA.
ObjectiveTo conduct a systematic review to evaluate in vitro functional properties of MSCs derived from patients with AA compared to healthy controls.
MethodsAccording to PRISMA guidelines, a comprehensive search strategy was performed by using online databases (Pubmed, ISI Web of Science, Embase, and the Cochrane Library). Studies reporting on phenotypical characterization, proliferation potential, differentiation capacity, immunomodulatory potential, and ability to support hematopoiesis were identified and screened using the Rayyan software tool.
Results23 articles were included in this systematic review, describing a total of 324 patients with AA and 285 controls. None of the studies identified a significant difference in expression of any MSC surface marker between both groups. However, AA-MSCs showed a decreased proliferation potential, an increased tendency to differentiate into the adipogenic lineage and decreased propensity towards osteogenic differentiation. Importantly, AA-MSCs show reduced capacity of immunosuppression and hematopoietic support in comparison to healthy controls.
ConclusionWe conclude that there are indications for a contribution of MSCs in the pathophysiology of AA. However, the current evidence is of poor quality and requires better defined study populations in addition to a more robust methodology to study MSC biology at a cellular and molecular level. Future studies on bone marrow microenvironment should aim at elucidating the interaction between MSCs, hematopoietic stem cells (HSCs) and immune cells to identify impairments associated with/causing BMF in patients with AA.

背景：在大多数再生障碍性贫血（aplastic anemia, AA）患者中，当前诊断仅能基于症状描述完成。由于对引发骨髓衰竭（bone marrow failure, BMF）的潜在病理生理机制缺乏深入认知，个体化治疗的开展受到了阻碍。此类患者中，通常认为自身免疫细胞介导的骨髓破坏是致病机制。近年来有研究提出，骨髓微环境的状态，尤其是间充质基质细胞（mesenchymal stromal cell, MSC）组分，可能在AA的病理生理过程中发挥潜在作用。因此，骨髓MSC的功能与免疫调节特性，或可成为AA诊疗的重要参考指标。
研究目的：开展一项系统综述，对比AA患者来源的MSC与健康对照者来源的MSC的体外功能特性。
研究方法：遵循系统综述与Meta分析优先报告条目（Preferred Reporting Items for Systematic Reviews and Meta-Analyses, PRISMA）指南，通过PubMed、ISI Web of Science、Embase及Cochrane图书馆等在线数据库开展全面检索。利用Rayyan软件工具，对报道MSC表型特征、增殖能力、分化潜能、免疫调节活性以及支持造血功能的相关研究进行筛选与纳入。
研究结果：本系统综述共纳入23篇文献，涉及324例AA患者与285例健康对照。现有研究均未发现两组MSC表面标志物表达存在显著差异。然而，AA来源的MSC增殖能力显著降低，成脂分化倾向增强，而成骨分化潜能则有所下降。尤为重要的是，与健康对照相比，AA来源的MSC免疫抑制与造血支持能力均出现显著降低。
研究结论：现有证据表明，MSC可能参与了AA的病理生理过程。但当前相关研究质量欠佳，未来需采用更严谨的研究方法，对研究人群进行更明确的界定，以在细胞与分子层面深入探究MSC的生物学特性。未来针对骨髓微环境的研究，应着重阐明MSC、造血干细胞（hematopoietic stem cell, HSC）与免疫细胞之间的相互作用，从而明确AA患者中与骨髓衰竭相关或导致骨髓衰竭的病理损伤机制。