ABSTRACT
Bone marrow-Multipotential stromal cells (BM-MSCs) are increasingly used to treat complicated fracture healing e.g., non-union. Though, the quality of these autologous cells is not well characterized. We aimed to evaluate bone healing-related capacities of non-union BM-MSCs. Iliac crest-BM was aspirated from long-bone fracture patients with normal healing (U) or non-united (NU). Uncultured (native) CD271highCD45low cells or passage-zero cultured BM-MSCs were analyzed for gene expression levels, and functional assays were conducted using culture-expanded BM-MSCs. Blood samples were analyzed for serum cytokine levels. Uncultured NU-CD271highCD45low cells significantly expressed fewer transcripts of growth factor receptors, EGFR, FGFR1, and FGRF2 than U cells. Significant fewer transcripts of alkaline phosphatase (ALPL), osteocalcin (BGLAP), osteonectin (SPARC) and osteopontin (SPP1) were detected in NU-CD271highCD45low cells. Additionally, immunoregulation-related markers were differentially expressed between NU- and U-CD271highCD45low cells. Interestingly, passage-zero NU BM-MSCs showed low expression of immunosuppressive mediators. However, culture-expanded NU and U BM-MSCs exhibited comparable proliferation, osteogenesis, and immunosuppression. Serum cytokine levels were found similar for NU and U groups. Collectively, native NU-BM-MSCs seemed to have low proliferative and osteogenic capacities; therefore, enhancing their quality should be considered for regenerative therapies. Further research on distorted immunoregulatory molecules expression in BM-MSCs could potentially benefit the prediction of complicated fracture healing.
Subject(s)
Fractures, Ununited/pathology , Gene Expression Profiling/methods , Gene Regulatory Networks , Mesenchymal Stem Cells/metabolism , Adult , Aged , Cell Culture Techniques , Cell Proliferation , Cells, Cultured , Cytokines/blood , Female , Fractures, Ununited/blood , Fractures, Ununited/genetics , Gene Expression Regulation , Humans , Male , Mesenchymal Stem Cells/cytology , Middle Aged , Phenotype , Young AdultABSTRACT
BACKGROUND: and purpose: We have undertaken a systematic review to evaluate the clinical results of intramedullary nailing (IMN) for open diaphyseal femoral fractures on the rates of union, delayed union, malunion, superficial and deep infection and bone grafting. METHODS: We searched the electronic databases of EMBASE, MEDLINE, from their inception until December 1st, 2017 with no language restrictions. The reference lists of all included articles and relevant reviews were also examined for potentially eligible studies. Hand search using electronic database of recent major orthopaedic journals was also carried. Two reviewers working independently extracted study characteristics and data to estimate the diagnostic odds ratio and 95% confidence interval for each result. RESULTS: Seventeen studies were eligible. Pooled estimate of effect size for union rate was 97% (95% CI: 94-99%). Deep infection rate was 6% (95% CI: 3-9.3%) and more prominent in Gustilo type III injuries; superficial infection was 5.6% (95% CI: 3-9.3%). Delayed union rate 3% (95% CI: 1-5.6%) while, malunion rate was 8.4% (95% CI: 5.7-11.6%). The need for bone grafting ranged from 0 to 9%. CONCLUSIONS: IMN remains the treatment of choice for open femoral diaphyseal fractures with very good union rates. Gustilo grade III injuries demonstrate a distinct higher deep infection rate and strict adherence to established surgical debridement and fixation protocols is advocated. The need for bone grafting can be as high as 9% and patients should be made aware of the possibility of requiring this additional procedure.
