Summary Stem cell regulation and hierarchical organization of human skeletal progenitors remain largely unexplored. Here, we report the isolation of a self-renewing and multipotent human skeletal stem cell (hSSC) that generates progenitors of bone, cartilage, and stroma, but not fat. Self-renewing and multipotent hSSCs are present in fetal and adult bones and can also be derived from BMP2-treated human adipose stroma (B-HAS) and induced pluripotent stem cells (iPSCs). Gene expression analysis of individual hSSCs reveals overall similarity between hSSCs obtained from different sources and partially explains skewed differentiation towards cartilage in fetal and iPSC-derived hSSCs. hSSCs undergo local expansion in response to acute skeletal injury. In addition, hSSC-derived stroma can maintain human hematopoietic stem cells (hHSCs) in serum-free culture conditions. Finally, we combine gene expression and epigenetic data of mouse skeletal stem cells (mSSCs) and hSSCs to identify evolutionarily conserved and divergent pathways driving SSC-mediated skeletogenesis.

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No standard criteria exist for diagnosing fracture nonunion, and studies suggest that assessment of fracture healing varies among orthopaedic surgeons. This variability can be problematic in both clinical and orthopaedic trauma research settings. An understanding of risk factors for nonunion and of diagnostic tests used to assess fracture healing can facilitate a systematic approach to evaluation and management. Risk factors for nonunion include medical comorbidities, age, and the characteristics of the injury. The method of fracture management also influences healing. Comprehensive evaluation includes an assessment of the patient's symptoms, signs, and immune and endocrine status as well as the biologic capacity of the fracture, presence of infection, and quality of reduction and fixation. Diagnostic tests include plain radiography, CT, ultrasonography, fluoroscopy, bone scan, MRI, and several laboratory tests, including assays for bone turnover markers in the peripheral circulation. A systematic approach to evaluating fracture union can help surgeons determine the timing and nature of interventions.

ABSTRACT. Objective. Delay in diagnosis of slipped capital femoral epiphysis (SCFE) has important implications in terms of slip severity and long-term hip outcome. The purpose of this study was to identify predictors of delay in the diagnosis of SCFE.Methods. A review of 196 patients with SCFE was performed. The primary outcome measure was delay from onset of symptoms to diagnosis. Covariates included age, gender, side, weight, pain location, insurance status, family income, slip severity, and slip stability. Delay in diagnosis was not normal in distribution; therefore, nonparametric univariate and multivariate analyses were performed.Results ABBREVIATION. SCFE, slipped capital femoral epiphysis.

Extracellular matrix (ECM) serves a key role in cell migration, attachment, and cell development. Here we report that ECM derived from human umbilical vein endothelial cells (HUVEC) promoted osteogenic differentiation of human bone marrow mesenchymal stem cells (hMSC). We first produced an HUVEC-derived ECM on a three-dimensional (3D) beta-tricalcium phosphate (β-TCP) scaffold by HUVEC seeding, incubation, and decellularization. The HUVEC-derived ECM was then characterized by SEM, FTIR, XPS, and immunofluorescence staining. The effect of HUVEC-derived ECM containing β-TCP scaffold on hMSC osteogenic differentiation was subsequently examined. SEM images indicate a dense matrix layer deposited on the surface of struts and pore walls. FTIR and XPS measurements show the presence of new functional groups (amide and hydroxyl groups) and elements (C and N) in the ECM/β-TCP scaffold when compared to the β-TCP scaffold alone. Immunofluorescence images indicate that high levels of fibronectin and collagen IV and low level of laminin were present on the scaffold. ECM-containing β-TCP scaffolds significantly increased alkaline phosphatase (ALP) specific activity and up-regulated expression of osteogenesis-related genes such as runx2, alkaline phosphatase, osteopontin and osteocalcin in hMSC, compared to β-TCP scaffolds alone. This increased effect was due to the activation of MAPK/ERK signaling pathway since disruption of this pathway using an ERK inhibitor PD98059 results in down-regulation of these osteogenic genes. Cell-derived ECM containing calcium phosphate scaffolds is a promising osteogenic-promoting bone void filler in bone tissue regeneration. Keywords: Extracellular matrix; HUVEC; hMSC; Osteogenesis; β-TCP