Larghero J, Farge D, Braccini A, Lecourt S, Scherberich A, Foïs E, Verrecchia F, Daikeler T, Gluckman E, Tyndall A, Bocelli-Tyndall C
Cell Therapy Unit, Assistance Publique-Hôpitaux de Paris, Saint-Louis Hospital, Paris, France.
Ann Rheum Dis. 2008 Apr;67(4):443-9. doi: 10.1136/ard.2007.071233. Epub 2007 May 25.
Mesenchymal stem cells (MSCs) have a potential immunomodulatory role in autoimmune disease; however, the qualitative properties and haematopoietic support capacity of MSCs derived from patients with autoimmune disease is unclear.
To further characterise phenotypically and functionally bone marrow (BM)-derived MSCs from patients with systemic sclerosis (SSc).
Key parameters of BM-derived MSC function and phenotype were assessed in 12 patients with SSc and compared with 13 healthy normal controls. The parameters included the ability to: form colony-forming unit fibroblasts (CFU-F), differentiate along the adipogenic and osteogenic lineages, express cell surface antigens defining the MSCs population, support normal haematopoiesis and suppress in vitro lymphocyte proliferation induced by either anti-CD3epsilon plus anti-CD28 monoclonal antibodies or the mixed lymphocyte reaction.
SSc MSCs were shown to have a similar characteristic phenotype, capacities to form CFU-F and to differentiate along adipogenic and osteogenic lineages as those of healthy donor MSCs. The ability of SSc MSCs to support long-term haematopoiesis was also identical to that of controls. Both healthy donor and SSc BM MSCs reduced the proliferation of autologous and allogeneic peripheral blood mononuclear cells in a cell number dependent fashion.
These results show that BM-derived MSCs from patients with SSc under the described culture conditions exhibit the same phenotypic, proliferative, differentiation potential and immunosuppressive properties as their healthy counterparts and could therefore be considered in an autologous setting. Further studies are needed to ensure the quality and safety of large-scale expansion of patient MSCs prior to their potential use in clinical trials.
间充质干细胞（MSC）在自身免疫性疾病中具有潜在的免疫调节作用；然而，来自自身免疫性疾病患者的MSC的定性特性和造血支持能力尚不清楚。
进一步从表型和功能上对系统性硬化症（SSc）患者骨髓来源的MSC进行特征描述。
评估了12例SSc患者骨髓来源的MSC功能和表型的关键参数，并与13名健康正常对照进行比较。这些参数包括：形成集落形成单位成纤维细胞（CFU-F）的能力、沿脂肪生成和成骨谱系分化的能力、表达定义MSC群体的细胞表面抗原的能力、支持正常造血的能力以及抑制由抗CD3ε加抗CD28单克隆抗体或混合淋巴细胞反应诱导的体外淋巴细胞增殖的能力。
SSc来源的MSC显示出与健康供体来源的MSC相似的特征性表型、形成CFU-F的能力以及沿脂肪生成和成骨谱系分化的能力。SSc来源的MSC支持长期造血的能力也与对照组相同。健康供体和SSc骨髓来源的MSC均以细胞数量依赖的方式降低了自体和异体外周血单个核细胞的增殖。
这些结果表明，在所述培养条件下，SSc患者骨髓来源的MSC表现出与其健康对应物相同的表型、增殖、分化潜能和免疫抑制特性，因此可在自体环境中予以考虑。在将患者来源的MSC用于临床试验之前，需要进一步研究以确保其大规模扩增的质量和安全性。
