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

Evidence for the Adverse Effect of Starvation on Bone Quality: A Review of the Literature

Malnutrition and starvation’s possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200–800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality

Reinforcing the role of the conventional C-arm - a novel method for simplified distal interlocking

<p>Abstract</p> <p>Background</p> <p>The common practice for insertion of distal locking screws of intramedullary nails is a freehand technique under fluoroscopic control. The process is technically demanding, time-consuming and afflicted to considerable radiation exposure of the patient and the surgical personnel. A new concept is introduced utilizing information from within conventional radiographic images to help accurately guide the surgeon to place the interlocking bolt into the interlocking hole. The newly developed technique was compared to conventional freehand in an operating room (OR) like setting on human cadaveric lower legs in terms of operating time and radiation exposure.</p> <p>Methods</p> <p>The proposed concept (guided freehand), generally based on the freehand gold standard, additionally guides the surgeon by means of visible landmarks projected into the C-arm image. A computer program plans the correct drilling trajectory by processing the lens-shaped hole projections of the interlocking holes from a single image. Holes can be drilled by visually aligning the drill to the planned trajectory. Besides a conventional C-arm, no additional tracking or navigation equipment is required.</p> <p>Ten fresh frozen human below-knee specimens were instrumented with an Expert Tibial Nail (Synthes GmbH, Switzerland). The implants were distally locked by performing the newly proposed technique as well as the conventional freehand technique on each specimen. An orthopedic resident surgeon inserted four distal screws per procedure. Operating time, number of images and radiation time were recorded and statistically compared between interlocking techniques using non-parametric tests.</p> <p>Results</p> <p>A 58% reduction in number of taken images per screw was found for the guided freehand technique (7.4 ± 3.4) (mean ± SD) compared to the freehand technique (17.6 ± 10.3) (<it>p </it>< 0.001). Total radiation time (all 4 screws) was 55% lower for the guided freehand technique compared to conventional freehand (<it>p </it>= 0.001). Operating time per screw (from first shot to screw tightened) was on average 22% reduced by guided freehand (<it>p </it>= 0.018).</p> <p>Conclusions</p> <p>In an experimental setting, the newly developed guided freehand technique for distal interlocking has proven to markedly reduce radiation exposure when compared to the conventional freehand technique. The method utilizes established clinical workflows and does not require cost intensive add-on devices or extensive training. The underlying principle carries potential to assist implant positioning in numerous other applications within orthopedics and trauma from screw insertions to placement of plates, nails or prostheses.</p

The Induction of APC with a Distinct Tolerogenic Phenotype via Contact-Dependent STAT3 Activation

BACKGROUND: Activation of the signal transducer and activator of transcription 3 (STAT3) within antigen presenting cells (APCs) is linked to abnormal APCs differentiation and function. We have previously shown that STAT3 is activated within APC by a novel contact-dependent mechanism, which plays a key role in mediating the immunomodulatory effects of hMSC. In order to better understand the underlying mechanisms that control APC maturation in a contact dependent manner, we extended our observation to tumor cells. Tumors were shown to secrete a variety of tumor-derived factors that activate STAT3 within infiltrating APCs. We now tested whether tumor cells can activate STAT3 within APC using the contact-dependent mechanism, in addition to soluble factors, and compared these two STAT3 activating pathways. PRINCIPAL FINDINGS: We demonstrate that in addition to tumor-derived secreted factors tumor cells activate STAT3 by a mechanism that is based on cell-cell interaction. We further demonstrate that these two STAT3 activating mechanisms differ in their JAK usage and their susceptibility to JSI-124 inhibition thereby representing two distinct pathways. Significantly, although both pathways activate STAT3, they modulate DCs maturation in a different manner that results in disparate phenotypic outcomes. Whereas the soluble-dependent pathway results in an immature phenotype, the contact-dependent pathway results in an apparently mature phenotype. Albeit their mature-like phenotype these latter cells express the tolerogenic markers ILT3 and ILT4 and possess T cell inhibitory activity. SIGNIFICANCE: This data suggests that, in at least certain cellular microenvironments, cell:cell interactions represent a novel way to activate STAT3 signaling, uncouple APC activation events and consequently regulate immunity and tolerance. Significantly, we have now demonstrated that this contact-dependent signaling pathway differs from that mediated by soluble factors and cytokines, inducing disparate phenotypic outcome, suggesting these two mechanisms have different and possibly complementary biological functions

Cigarette Smoking Is Associated with a Lower Concentration of CD105+ Bone Marrow Progenitor Cells

Cigarette smoking is associated with musculoskeletal degenerative disorders, delayed fracture healing, and nonunion. Bone marrow progenitor cells (BMPCs), known to express CD105, are important in local trophic and immunomodulatory activity and central to musculoskeletal healing/regeneration. We hypothesized that smoking is associated with lower levels of BMPC. Iliac bone marrow samples were collected from individuals aged 18–65 years during the first steps of pelvic surgery, under IRB approval with informed consent. Patients with active infectious or neoplastic disease, a history of cytotoxic or radiation therapy, primary or secondary metabolic bone disease, or bone marrow dysfunction were excluded. Separation process purity and the number of BMPCs recovered were assessed with FACS. BMPC populations in self-reported smokers and nonsmokers were compared using the two-tailed t-test. 13 smokers and 13 nonsmokers of comparable age and gender were included. The average concentration of BMPCs was 3.52 × 105/mL ± 2.45 × 105/mL for nonsmokers versus 1.31 × 105/mL ± 1.61 × 105/mL for smokers (t= 3.2, P=0.004). This suggests that cigarette smoking is linked to a significant decrease in the concentration of BMPCs, which may contribute to the reduced regenerative capacity of smokers, with implications for musculoskeletal maintenance and repair

The epidemiology of wrist and hand injury in two hospitals in Jerusalem: substantial differences between population subgroups

Abstract Background Wrist and hand injuries are common and constitute a major economic burden. General injury prevention programs have failed to demonstrate a decrease in injury rates. We hypothesized that there are differences in injury patterns in culturally diverse subpopulations of a metropolitan area treated within the same medical system, which may partly explain the difficulties associated with injury prevention. Methods We conducted a survey of patients admitted to emergency departments of two hospitals in Jerusalem for wrist and hand injuries during a 3 month period. Patients were asked to complete a questionnaire regarding demographic data, injury type and mechanism. Injury type and mechanism were then compared for age, gender, level of education and degree of religiosity. Results The questionnaire was completed by 799 patients (response rate 62%; 75% male; average age 27). Thirty-one percent reported they were injured at work, 33% at home and 36% during leisure activities. Data analysis showed that several subpopulations were found to be at risk as compared to their corresponding groups and relative proportion in the overall population of the city. These included contusions after falls in non-ultra-Orthodox Jewish women aged 65 years and over, crush injuries in ultra-Orthodox Jews under the age of 10 (53% vs. 14% for non ultra-Orthodox Jews, respectively) and Muslim teens. Muslims were injured more, especially at work, in comparison to their relative proportion in the population as a whole. Conclusion Different subpopulations at risk and different injury patterns of wrist and hand injuries were found in this culturally heterogeneous population. Awareness of these differences may be the first step when designing specific injury prevention programs in a culturally diverse population. A combined effort of community leaders and government agencies is needed to deal with the specific populations at risk, although legislation may be needed to limit some of the risks such as teens and specific work related hazards and exposures

The effect of shoe gear on human tibial strains recorded during dynamic loading: A pilot study

The study was conducted to test the hypothesis that alterations in shoe gear can affect tibial strains in the human during dynamic loading. Rosette strain gauges were mounted on the medial border of the mid-diaphysis in two human subjects with a new strain gauge bonding technique using methyl methacrylate. Strain measurements were made at this site, the most frequent location for stress fractures in the Israeli Army during treadmill walking and free running while wearing various sport shoes (Rockport ProWalkers and New Balance NBX 900) and army boots (light Israeli infantry, double layered sole israeli infantry, and Zohar Infantry boots). Data were analyzed for only one of the subjects because strain gauge bonding was found to be inadequate at the time of surgical removal in the other subject. No single shoe lowered both the principal tibial compression and tensile strains, and the shear strains. The Zohar boot had the lowest principal compression strains during treadmill walking and mobile running, despite its relatively higher weight and sole durometry