Highlights d Mx1 and aSMA combination selectively labels SSCs resident in adult periosteum (P-SSC) d Mx1 + aSMA + P-SSCs are long-term repopulating and functionally distinct SSCs d Mx1 + aSMA + P-SSCs and human P-SSCs specifically express the CCL5 receptor CCR5 d CCL5 induces P-SSC migration in vivo, and its loss delays bone healing

Periosteum and bone marrow (BM) both contain skeletal stem/progenitor cells (SSCs) that participate in fracture repair. However, the functional difference and selective regulatory mechanisms of SSCs in different locations are unknown due to the lack of specific markers. Here, we report a comprehensive gene expression analysis of bone marrow SSCs (BM-SSCs), periosteal SSCs (P-SSCs), and more differentiated osteoprogenitors by using reporter mice expressing Interferon-inducible Mx1 and NestinGFP, previously known SSC markers. We first defined that the BM-SSCs can be enriched by the combination of Mx1 and NestinGFP expression, while endogenous P-SSCs can be isolated by positive selection of Mx1, CD105 and CD140a (known SSC markers) combined with the negative selection of CD45, CD31, and osteocalcinGFP (a mature osteoblast marker). Comparative gene expression analysis with FACS-sorted BM-SSCs, P-SSCs, Osterix+ preosteoblasts, CD51+ stroma cells and CD45+ hematopoietic cells as controls revealed that BM-SSCs and P-SSCs have high similarity with few potential differences without statistical significance. We also found that CD51+ cells are highly heterogeneous and have little overlap with SSCs. This was further supported by the microarray cluster analysis, where the two SSC populations clustered together but are separate from the CD51+ cells. However, when comparing SSC population to controls, we found several genes that are uniquely upregulated in endogenous SSCs. Amongst these genes, we found KDR (aka Flk1 or VEGFR2) to be most interesting and discovered that it is highly and selectively expressed in P-SSCs. This finding suggests that endogenous P-SSCs are functionally very similar to BM-SSCs with undetectable significant differences in gene expression but there are distinct molecular signatures in P-SSCs, which can be useful to specify P-SSC subset in vivo.

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12Periosteum and bone marrow (BM) to controls, we found several genes that were uniquely upregulated in endogenous SSCs. 28Amongst these genes, we found KDR (aka Flk1 or VEGFR2) to be most interesting and 29 discovered that it is highly and selectively expressed in P-SSCs. This finding suggests that 30 endogenous P-SSCs are functionally very similar to BM-SSCs with undetectable significant 31 differences in gene expression but there are distinct molecular signatures in P-SSCs, which can 32 be useful to specify P-SSC subset in vivo. 33peer-reviewed)

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Background: Consensus is lacking regarding the lengthening procedures in magnetically controlled growing rods (MCGR), and no studies have compared the outcome between different distraction principles. The purpose of the present study was to compare distraction-to-stall with targeted distraction and identify variables associated with achieved distraction. Methods: We performed a 2-center retrospective study of all children treated with MCGR from November 2013 to January 2019, having a minimum of 1-year follow-up and undergoing a minimum of 3 distractions. Exclusion criteria were single-rod constructs and conversion cases. In group 1 (21 patients), we used a distraction-to-stall (maximum force) principle where each rod was lengthened until the internal magnetic driver stopped (clunking). In group 2 (18 patients), we used a targeted distraction principle, where the desired distraction was entered the remote control before distraction. In both groups we aimed for maximal distraction and curve correction at index surgery. Achieved distraction was measured on calibrated radiographs and compared between the 2 groups using a linear mixed effects model. Univariate and multivariate analyses were performed to identify variables associated with achieved distraction within the first year. Results: Mean age at surgery was 9.5±2.0 years. Etiology of the deformity was congenital/structural (n=7), neuromuscular (n=9), syndromic (n=3), or idiopathic (n=20). Demographics and preoperative characteristics including spinal height (T1T12 and T1S1) did not differ significantly between the groups (P≥0.13). Time interval between distractions were mean 18 days (95% confidence interval: 10-25) shorter in group 1. Implant-related complications occurred in 10/39 patients, 5 in each group. We found no difference in achieved distraction between the groups in the linear mixed effects model. In the multivariate analysis, preoperative major curve angle was the only independent variable associated with achieved distraction. Conclusions: In 2 comparable and consecutive cohorts of patients treated with MCGR, we found no difference in achieved distraction between a distraction-to-stall and a targeted distraction principle. Preoperative major curve angle was the only independent predictor of achieved distraction. Level of Evidence: Level III—retrospective comparative study.

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Nonidiopathic scoliosis encompasses a group of diagnoses, including neuromuscular scoliosis, syndromic scoliosis and congenital scoliosis. The objective of this study was to compare the preoperative and postoperative clinical differences in pediatric nonidiopathic scoliosis patients with neuromuscular scoliosis vs. syndromic scoliosis/congenital scoliosis. This is a single-center retrospective review of all pediatric patients undergoing spinal instrumentation for nonidiopathic scoliosis during a 5-year period. Neuromuscular scoliosis patients (n = 144), syndromic scoliosis patients (n = 44) and congenital scoliosis patients (n = 52) were compared. Demographics, patient characteristics and outcomes were compared. Neuromuscular scoliosis patients had lower BMI z-scores and were more likely to have pulmonary disease, technology dependence and seizure disorder. Additionally, neuromuscular scoliosis patients underwent bigger procedures with more levels fused and a higher rate of pelvis fixation. By direct comparison, neuromuscular scoliosis patients tended to have more complications including deep surgical site infections, readmission in 30 days, return to operating room in 90 days and emergency care visits in 90 days. When controlling for the differences in their preexisting conditions and surgical procedure, we found that pelvic fixation was a major confounding factor, whereas the others had no effect. We further subanalyzed cerebral palsy patients and found this group to exhibit no difference in complications compared to other neuromuscular scoliosis subtypes. Neuromuscular scoliosis patients have different characteristics and subsequent postoperative complications than those with syndromic scoliosis and congenital scoliosis. The difference in complication profile is mainly due to differences in surgical procedure and a higher rate of pelvic fixation. This should be considered when planning nonidiopathic scoliosis surgery among multidisciplinary teams.