title: Isolation and Characterization of Multipotential Mesenchymal Stromal Cells from Congenital Pseudoarthrosis of the Tibia: Case Report.
abstract: 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.
authors.affiliation: 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.
authors.forename: Dylana
authors.initials: D
authors.lastname: Diaz-Solano
authors.affiliation: 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.
authors.forename: Olga
authors.initials: O
authors.lastname: Wittig
authors.affiliation: Instituto de Anatomopatología, Universidad Central de Venezuela, Caracas, 1080, Venezuela.
authors.forename: Jose D
authors.initials: JD
authors.lastname: Mota
authors.affiliation: 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.
authors.forename: Jose E
authors.initials: JE
authors.lastname: Cardier
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002675:Child, Preschool; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D011542:Pseudarthrosis / Q000151:congenital* / Q000000981:diagnostic imaging / Q000601:surgery; D011859:Radiography; D013977:Tibia / Q000166:cytology* / Q000000981:diagnostic imaging / Q000502:physiology*
keywords: MSC; congenital; pseudoarthrosis; tibia