Developing stem cell-based therapeutic strategies in orthopaedic surgery

open5siEDITORIAL - Developing Stem Cell-Based Therapeutic Strategies in Orthopaedic SurgeryopenAtesok, Kivanc; Ochi, Mitsuo; Baldini, Nicola; Schemitsch, Emil; Liebergall, MeirAtesok, Kivanc; Ochi, Mitsuo; Baldini, Nicola; Schemitsch, Emil; Liebergall, Mei

Current Strategies in Prevention of Postoperative Infections in Spine Surgery.

Study Design: Narrative review. Objectives: Postoperative surgical site infections (SSIs) are among the most common acute complications in spine surgery and have a devastating impact on outcomes. They can lead to increased morbidity and mortality as well as greater economic burden. Hence, preventive strategies to reduce the rate of SSIs after spine surgery have become vitally important. The purpose of this article was to summarize and critically analyze the available evidence related to current strategies in the prevention of SSIs after spine surgery. Methods: A literature search utilizing Medline database was performed. Relevant studies from all the evidence levels have been included. Recommendations to decrease the risk of SSIs have been provided based on the results from studies with the highest level of evidence. Results: SSI prevention occurs at each phase of care including the preoperative, intraoperative, and postoperative periods. Meticulous patient selection, tight glycemic control in diabetics, smoking cessation, and screening/eradication of Conclusions: Although preventive strategies are already in use alone or in combination, further high-level research is required to prove their efficacy in reducing the rate of SSIs in spine surgery before evidence-based standard infection prophylaxis guidelines can be built

The Use of Endothelial Progenitor Cells for the Regeneration of Musculoskeletal and Neural Tissues

Endothelial progenitor cells (EPCs) derived from bone marrow and blood can differentiate into endothelial cells and promote neovascularization. In addition, EPCs are a promising cell source for the repair of various types of vascularized tissues and have been used in animal experiments and clinical trials for tissue repair. In this review, we focused on the kinetics of endogenous EPCs during tissue repair and the application of EPCs or stem cell populations containing EPCs for tissue regeneration in musculoskeletal and neural tissues including the bone, skeletal muscle, ligaments, spinal cord, and peripheral nerves. EPCs can be mobilized from bone marrow and recruited to injured tissue to contribute to neovascularization and tissue repair. In addition, EPCs or stem cell populations containing EPCs promote neovascularization and tissue repair through their differentiation to endothelial cells or tissue-specific cells, the upregulation of growth factors, and the induction and activation of endogenous stem cells. Human peripheral blood CD34(+) cells containing EPCs have been used in clinical trials of bone repair. Thus, EPCs are a promising cell source for the treatment of musculoskeletal and neural tissue injury

Expression of VEGF gene isoforms in a rat segmental bone defect model treated with EPCs

Angiogenesis and osteogenesis are essential for bone growth, fracture repair, and bone remodeling. Vascular endothelial growth factor (VEGF) has an important role in bone repair by promoting angiogenesis and osteogenesis. In our previous study, endothelial progenitor cells (EPCs) promoted bone healing in a rat segmental bone defect as confirmed by radiological, histological, biomechanical and microCT evaluations. While EPCs have demonstrated effectiveness in animal models of fracture healing, the mechanism by which EPCs enhance fracture healing remains unclear. We hypothesized a possible paracrine mechanism of action, where the secretion of growth factors critical to the processes of fracture healing (such as VEGF), is responsible for the positive effects of EPC therapy. The purpose of this study was to evaluate VEGF gene expression after local EPC therapy for a rat segmental bone defect. Methods: Rat bone marrow-derived EPCs were isolated by the Ficoll-paque gradient centrifuge technique. The EPCs were cultured for 7 to 10 days in endothelial cell growth medium with supplements and collected for treatment of the rat segmental bone defect. EPCs were identified by immunocytochemistry staining with primary antibodies for CD34, CD133, FLK-1, and vWF. A total of fifty six rats were studied. A five millimeter segmental bone defect was created in the middle 1/3 of each femur followed by mini plate fixation. The treatment group received 1x106 EPCs locally at the bone defect on a gelfoam scaffold and control animals received the gelfoam scaffold only. Seven control and seven EPC treated rats were included in each group at 1, 2, 3 and 10 weeks. Animals were sacrificed at the end of the treatment period, and specimens from the fracture gap 4 area were collected and immediately frozen. Rat VEGF mRNA was measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and quantified by VisionWorksLS. All measurements were performed in triplicate. Results: Cultured EPCs at 1 week showed positive staining for CD34, CD133, Flk-1 and vWf markers. The EPC group had a greater VEGF expression than the control group at weeks 1, 2 and 3, but not at week 10. Three VEGF isoforms were detected in this rat model: VEGF120, VEGF164 and VEGF188. VEGF120 and VEGF164 levels peaked at two weeks, while VEGF188 levels peaked at three weeks. All three VEGF isoform levels were low at ten weeks. Discussion and Conclusion: EPC-based therapy for a segmental bone defect results in increased VEGF expression during the early period of fracture repair. In addition, the specific VEGF isoform may be a key regulator of the bone healing process. These findings demonstrate that EPCs may promote fracture healing by increasing VEGF levels and thus stimulating angiogenesis, a process that is essential for early callus formation and bone regeneration

Pathology and Treatment of Traumatic Cervical Spine Syndrome: Whiplash Injury

Traumatic cervical syndrome comprises the various symptoms that occur as a result of external force such as that of a traffic accident. In 1995, the Quebec Task Force on whiplash-associated disorders (WAD) formulated the Quebec classification, with accompanying clinical practice guidelines. These guidelines were in accordance with the stated clinical isolated or combined symptoms of the syndrome: neck pain, headaches, dizziness, numbness of head or face, eye pain, vision loss, double vision, tinnitus, hearing loss, nausea, and numbness and/or weakness of extremities. In recent years, cerebrospinal fluid hypovolemia or fibromyalgia has been recognized as a major notable cause of a variety of symptoms, although many clinical questions remain regarding the pathology of this syndrome. Therefore, its diagnosis and treatment should be conducted extremely carefully. While the Quebec classification and its guidelines are very useful for the normalization and standardization of symptoms of traumatic cervical syndrome, in the future, we would like to see the emergence of new guidelines that better address the diversity of this disease

Traumatic Lumbosacral Dislocation: Current Concepts in Diagnosis and Management

Traumatic lumbosacral dislocation is a rare, high-energy mechanism injury characterized by displacement of the fifth lumbar vertebra in relation to the sacrum. Due to the violent trauma typically associated with this lesion, there are often severe, coexisting injuries. High-quality radiographic studies, in addition to appropriate utilization of CT scan and MRI, are essential for proper evaluation and diagnosis. Although reports in the literature include nonoperative and operative management, most authors advocate for surgical treatment with open reduction and decompression with instrumentation and fusion. Despite advances in early diagnosis and management, this injury type is associated with significant morbidity and mortality, and long-term patient outcomes remain unclear

Posttraumatic Spinal Cord Injury without Radiographic Abnormality

“Spinal Cord Injury without Radiographic Abnormality” (SCIWORA) is a term that denotes objective clinical signs of posttraumatic spinal cord injury without evidence of fracture or malalignment on plain radiographs and computed tomography (CT) of the spine. SCIWORA is most commonly seen in children with a predilection for the cervical spinal cord due to the increased mobility of the cervical spine, the inherent ligamentous laxity, and the large head-to-body ratio during childhood. However, SCIWORA can also be seen in adults and, in rare cases, the thoracolumbar spinal cord can be affected too. Magnetic resonance imaging (MRI) has become a valuable diagnostic tool in patients with SCIWORA because of its superior ability to identify soft tissue lesions such as cord edema, hematomas and transections, and discoligamentous injuries that may not be visualized in plain radiographs and CT. The mainstay of treatment in patients with SCIWORA is nonoperative management including steroid therapy, immobilization, and avoidance of activities that may increase the risk of exacerbation or recurrent injury. Although the role of operative treatment in SCIWORA can be controversial, surgical alternatives such as decompression and fusion should be considered in selected patients with clinical and MRI evidence of persistent spinal cord compression and instability

Stem cells in degenerative orthopaedic pathologies: effects of aging on therapeutic potential

© 2015 European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA) Purpose: The purpose of this study was to summarize the current evidence on the use of stem cells in the elderly population with degenerative orthopaedic pathologies and to highlight the pathophysiologic mechanisms behind today’s therapeutic challenges in stem cell-based regeneration of destructed tissues in the elderly patients with osteoarthritis (OA), degenerative disc disease (DDD), and tendinopathies.Methods: Clinical and basic science studies that report the use of stem cells in the elderly patients with OA, DDD, and tendinopathies were identified using a PubMed search. The studies published in English have been assessed, and the best and most recent evidence was included in the current study. Results: Evidence suggests that, although short-term results regarding the effects of stem cell therapy in degenerative orthopaedic pathologies can be promising, stem cell therapies do not appear to reverse age-related tissue degeneration. Causes of suboptimal outcomes can be attributed to the decrease in the therapeutic potential of aged stem cell populations and the regenerative capacity of these cells, which might be negatively influenced in an aged microenvironment within the degenerated tissues of elderly patients with OA, DDD, and tendinopathies. Conclusions: Clinical protocols guiding the use of stem cells in the elderly patient population are still under development, and high-level randomized controlled trials with long-term outcomes are lacking. Understanding the consequences of age-related changes in stem cell function and responsiveness of the in vivo microenvironment to stem cells is critical when designing cell-based therapies for elderly patients with degenerative orthopaedic pathologies