The use of bone morphogenetic protein in lumbar spine surgery.

Creating a solid lumbar spinal fusion remains a challenge. Despite advances in fixation, a pseudarthrosis still may occur. Recently, attention has focused on creating a more biologically favorable environment to enhance fusion rate. Bone morphogenetic proteins (BMPs) are a group of secreted growth factors that belong to the transforming growth factor-beta superfamily. Two recombinant BMP proteins, rhBMP-2 and rhBMP-7 (OP-1), have been used successfully in preclinical and clinical trials and are commercially available for clinical applications.

Adjacent segment disease after cervical spine fusion.

Anterior cervical diskectomy and fusion is one of the most common cervical spine procedures. Although it is usually successful in relieving the symptoms of radiculopathy and myelopathy, the subsequent development of clinically significant disk disease at levels adjacent to the fusion is a matter of concern. Adjacent segment cervical disease occurs in approximately 3% of patients; the incidence is expected to increase to more than 25% of patients within the first 10 years after the index fusion procedure. The disease is well described in the literature, and significant basic science and clinical research has been conducted. Nonetheless, the cause of the disease is a matter of debate. A combination of factors probably contributes to its development, including the increased biomechanical stress placed on the disk space adjacent to a fusion and the natural history of cervical spondylosis in patients known to have such pathology. Clinical and biomechanical data are available to support each of these claims. Symptomatic disk disease adjacent to a cervical fusion is a significant clinical problem, and, therefore, motion-sparing technology has been developed to reduce its incidence. Two cervical disk replacement systems are currently approved by the US Food and Drug Administration for the treatment of symptomatic cervical spondylosis.

Regenerative medicine for the musculoskeletal system based on muscle-derived stem cells.

The identification and characterization of stem cells is introducing a paradigm shift in the field of orthopaedic surgery. Whereas in the past, diseased tissue was replaced with allograft material, current trends in research revolve around regenerating damaged tissue. Muscle-derived stem cells have an application in regeneration of articular cartilage, bone, and skeletal muscle. These postnatal (ie, adult) stem cells can be readily isolated via muscle biopsy. They can display long-term proliferation, high self-renewal, and multipotent differentiation. They also can be genetically modified to secrete growth factors important to tissue healing, thereby functioning as implantable, long-lasting reservoirs for these molecules. Taken together, this evidence suggests that muscle-derived stem cells are well suited for gene therapy and tissue engineering applications for the musculoskeletal system. Effective implementation of even just a few applications of muscle-derived stem cell-based tissue engineering has the potential to revolutionize the way certain musculoskeletal diseases are managed.

Does open reduction increase the chance of infection during intramedullary nailing of closed tibial shaft fractures?

OBJECTIVE: To evaluate whether an open technique used to obtain reduction during intramedullary nailing of closed tibial shaft fractures increases the risk of infection, compared to closed reduction and nailing. SETTING: University level 1 trauma center. DESIGN: Retrospective database analysis. PATIENTS/PARTICIPANTS: One hundred seventeen patients with 119 fractures from our trauma database who had sufficient follow-up and met study criteria. The patients were grouped by open versus closed reduction. Only OTA fracture types 42 A to C were included in this study. INTERVENTION: Locked reamed intramedullary nailing for closed tibial shaft fractures accomplished through either open or closed reduction. MAIN OUTCOME MEASUREMENT: The presence or absence of infection as determined by the clinical presentation (erythema, warmth, purulent drainage, fevers, chills, increased pain at the fracture site), indicative laboratory work (complete blood count, erythrocyte sedimentation rate, C-reactive protein), and/or positive culture. RESULTS: There were 85 males and 32 females. The average age was 35.7 years; the average follow-up was 14.3 months. Of the 119 fractures, 79 had closed reduction whereas 40 had open reduction. The open reductions consisted of 13 with a formal incision (>1 cm in length), 22 with percutaneous incisions, and 5 with fasciotomies. There were no infections in the closed reduction group and 2 infections (5%) in the open reduction group. This difference was not statistically significant (P=0.1). The average time to union was 7.0 months in closed reductions and 7.3 months in open reductions. By latest follow-up, 107 fractures had reached union (89.9%), 1 had not (0.8%), and 11 were lost to final follow-up (9.2%). CONCLUSIONS: Limited open techniques can greatly facilitate the reduction of closed tibial shaft fractures but raise concern for infection through exposure of the fracture site. This study found that the rate of infection for open versus closed reductions was higher but not statistically different. Judicious use of open reduction techniques during intramedullary nailing of closed tibia fractures seems to have a minimal risk of infection.

The role of CD34 expression and cellular fusion in the regeneration capacity of myogenic progenitor cells.

Characterization of myogenic subpopulations has traditionally been performed independently of their functional performance following transplantation. Using the preplate technique, which separates cells based on their variable adhesion characteristics, we investigated the use of cell surface proteins to potentially identify progenitors with enhanced regeneration capabilities. Based on previous studies, we used cell sorting to investigate stem cell antigen-1 (Sca-1) and CD34 expression on myogenic populations with late adhesion characteristics. We compared the regeneration efficiency of these sorted progenitors, as well as those displaying early adhesion characteristics, by quantifying their ability to regenerate skeletal muscle and restore dystrophin following transplantation into allogenic dystrophic host muscle. Identification and utilization of late adhering populations based on CD34 expression led to differential regeneration, with CD34-positive populations exhibiting significant improvements in dystrophin restoration compared with both their CD34-negative counterparts and early adhering cell populations. Regenerative capacity was found to correspond to the level of myogenic commitment, defined by myogenic regulatory factor expression, and the rate and degree of induced cell differentiation and fusion. These results demonstrate the ability to separate definable subpopulations of myogenic progenitors based on CD34 expression and reveal the potential implications of defining myogenic cell behavioral and phenotypic characteristics in relation to their regenerative capacity in vivo.

Identification of a novel population of muscle stem cells in mice: potential for muscle regeneration.

Three populations of myogenic cells were isolated from normal mouse skeletal muscle based on their adhesion characteristics and proliferation behaviors. Although two of these populations displayed satellite cell characteristics, a third population of long-time proliferating cells expressing hematopoietic stem cell markers was also identified. This third population comprises cells that retain their phenotype for more than 30 passages with normal karyotype and can differentiate into muscle, neural, and endothelial lineages both in vitro and in vivo. In contrast to the other two populations of myogenic cells, the transplantation of the long-time proliferating cells improved the efficiency of muscle regeneration and dystrophin delivery to dystrophic muscle. The long-time proliferating cells' ability to proliferate in vivo for an extended period of time, combined with their strong capacity for self-renewal, their multipotent differentiation, and their immune-privileged behavior, reveals, at least in part, the basis for the improvement of cell transplantation. Our results suggest that this novel population of muscle-derived stem cells will significantly improve muscle cell-mediated therapies.