Atmar Khaled, Tulling Adam J, Lankester Arjan C, Bartels Marije, Smiers Frans J, van der Burg Mirjam, Mohseny Alexander B
Department of Pediatric Hematology and Stem Cell Transplantation, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, Netherlands.
Department of Pediatric Hematology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, Netherlands.
Front Immunol. 2022 Mar 9;13:859668. doi: 10.3389/fimmu.2022.859668. eCollection 2022.
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 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.
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。由于对导致骨髓衰竭（BMF）的潜在病理生理机制缺乏了解，阻碍了针对性治疗。在这些患者中，骨髓的自身免疫细胞介导的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病理生理学中的一个潜在因素。因此，骨髓间充质干细胞的功能和免疫调节特性可能是AA的重要参数。
进行一项系统评价，以评估与健康对照相比，AA患者来源的间充质干细胞的功能特性。
根据PRISMA指南，通过使用在线数据库（PubMed、ISI Web of Science、Embase和Cochrane图书馆）进行全面的检索策略。使用Rayyan软件工具识别和筛选报告表型特征、增殖潜力、分化能力、免疫调节潜力和支持造血能力的研究。
本系统评价纳入了23篇文章，共描述了324例AA患者和285例对照。没有一项研究发现两组间任何间充质干细胞表面标志物的表达有显著差异。然而，AA-MSC显示出增殖潜力降低，向脂肪生成谱系分化的趋势增加，向成骨分化的倾向降低。重要的是，与健康对照相比，AA-MSC的免疫抑制和造血支持能力降低。
我们得出结论，有迹象表明间充质干细胞在AA的病理生理学中起作用。然而，目前的证据质量较差，除了需要更强大的方法在细胞和分子水平研究间充质干细胞生物学外，还需要定义更明确的研究人群。未来关于骨髓微环境的研究应旨在阐明间充质干细胞、造血干细胞（HSC）和免疫细胞之间的相互作用，以确定与AA患者BMF相关/导致BMF的损伤。
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