在大多数再生障碍性贫血(AA)患者中,诊断仅限于对症状的描述。对导致骨髓衰竭(BMF)的潜在病理生理机制缺乏了解,礼篮量身定制的治疗。在这些患者中,自身免疫细胞介导的骨髓破坏通常被认为是致病机制。骨髓微环境的状态,特别是间充质基质细胞(MSC)成分,最近被认为是AA病理生理学的潜在参与者。因此,功能,骨髓间充质干细胞的免疫调节特性可能代表AA的重要参数。
进行系统评价以评价来自AA患者的MSC与健康对照的体外功能特性。
根据PRISMA指南,通过使用在线数据库(Pubmed,ISIWebofScience,Embase,和Cochrane图书馆)。报告表型特征的研究,扩散潜力,分化能力,免疫调节潜能,使用Rayyan软件工具鉴定和筛选支持造血的能力。
本系统综述包括23篇文章,描述了总共324例AA患者和285例对照。没有一项研究发现两组间任何MSC表面标记物的表达存在显著差异。然而,AA-MSCs的增殖潜能降低,分化为成脂谱系的趋势增加,成骨分化的倾向降低。重要的是,与健康对照相比,AA-MSC显示降低的免疫抑制和造血支持能力。
我们得出结论,有迹象表明MSCs在AA的病理生理学中起作用。然而,目前的证据质量较差,除了在细胞和分子水平上研究MSC生物学的更可靠的方法外,还需要更明确的研究群体.未来对骨髓微环境的研究应旨在阐明MSCs之间的相互作用,造血干细胞(HSC)和免疫细胞,以确定与AA患者BMF相关/引起的损伤。
In 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.
To conduct a systematic review to evaluate in vitro functional properties of MSCs derived from patients with AA compared to healthy controls.
According 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.
23 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.
We 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.