Diaz-Solano Dylana, Wittig Olga, Mota Jose D, Cardier Jose E
Unidad de Terapia Celular-Laboratorio de Patología Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas (IVIC), Apartado 21827, Caracas, 1020-A, Venezuela.
Instituto de Anatomopatología, Universidad Central de Venezuela, Caracas, 1080, Venezuela.
Anat Rec (Hoboken). 2015 Oct;298(10):1804-14. doi: 10.1002/ar.23198. Epub 2015 Jul 30.
Congenital pseudoarthrosis of the tibia (CPT) is an uncommon disease whose etiology and pathogenesis is unknown. Several evidences suggest that decreased osteogenic capacities, impaired local vascularization, and microenvironment alterations may play a role in the pathogenesis of CPT. Additionally, it is not clear if the pathogenesis of this disease is related to the absence of cells with osteogenic capacity of differentiation. In this work, a two-year-old patient diagnosed with CPT underwent an orthopedic surgery to promote bone union in a pseudoarthrosis lesion. Tissue from CPT lesion was excised, and histological evaluation and tissue culture were performed. Histologic analysis of the soft CPT lesion showed the presence of highly cellular fibrous tissue, vascularization, and abundant extracellular matrix. Fusiform cells of mesenchymal appearance were observed but osteoblasts, osteoclasts, chondrocytes, and adipose cells were not found. There was no evidence of osteogenesis. CPT tissue cultured as explants showed, after one month of culture, evidence of osteogenesis, chondrogenesis, and adipogenesis. Cells isolated from explants of CPT tissue showed a fibroblast-like morphology and expressed the mesenchymal stromal cell (MSC) markers: CD105, CD73, and CD90 (CPT-MSC). Functional analysis showed that CPT-MSC differentiate, in vitro, into osteogenic, chondrogenic, and adipocytic cells. CPT-MSC expressed osteocalcin and agrecan. CPT-MSC produced collagen in the presence of ascorbic acid. MSC from BM of normal individuals were used as control. In summary, our results indicate that CPT tissue contains MSC with osteogenic capacity of differentiation. It is possible that CPT microenvironment may contribute to impair the osteogenic capacity of differentiation of CPT-MSC.
先天性胫骨假关节(CPT)是一种罕见疾病,其病因和发病机制尚不清楚。多项证据表明,成骨能力下降、局部血管化受损和微环境改变可能在CPT的发病机制中起作用。此外,这种疾病的发病机制是否与缺乏具有成骨分化能力的细胞有关尚不清楚。在这项研究中,一名两岁的CPT患者接受了骨科手术,以促进假关节病变处的骨愈合。切除了CPT病变组织,并进行了组织学评估和组织培养。对CPT软性病变的组织学分析显示存在高度细胞化的纤维组织、血管化和丰富的细胞外基质。观察到具有间充质外观的梭形细胞,但未发现成骨细胞、破骨细胞、软骨细胞和脂肪细胞。没有成骨的证据。作为外植体培养的CPT组织在培养一个月后显示有成骨、软骨生成和脂肪生成的证据。从CPT组织外植体中分离出的细胞呈现成纤维细胞样形态,并表达间充质基质细胞(MSC)标志物:CD105、CD73和CD90(CPT-MSC)。功能分析表明,CPT-MSC在体外可分化为成骨、软骨生成和脂肪细胞。CPT-MSC表达骨钙素和聚集蛋白聚糖。CPT-MSC在抗坏血酸存在下产生胶原蛋白。将正常个体骨髓中的MSC用作对照。总之,我们的结果表明CPT组织含有具有成骨分化能力的MSC。CPT微环境可能会损害CPT-MSC的成骨分化能力。