Undifferentiated human mesenchymal stem cells (hMSCs) are highly sensitive to mechanical strain: transcriptionally controlled early osteo-chondrogenic response in vitro

SummaryObjectivePhysical cues play a crucial role in skeletogenesis and osteochondral regeneration. Although human mesenchymal stem cells (hMSCs) offer considerable therapeutic potential, little is known about the molecular mechanisms that control their differentiation. We hypothesized that mechanical strain might be an inherent stimulus for chondrogenic and/or osteogenic differentiation in undifferentiated hMSCs, where c-Fos (FOS) might play a major role in mechanotransduction.MethodhMSCs from 10 donors were intermittently stimulated by cyclic tensile strain (CTS) at 3000 μstrain for a period of 3 days. Differential gene expression of strained and unstrained hMSCs was analysed by real-time RT-PCR for several marker genes, including the transcription factors FOS, RUNX2, SOX9, and others. Additionally, alkaline phosphatase activity (ALP) was determined kinetically.ResultsThe application of CTS significantly stimulated the expression levels of the early chondrogenic and osteogenic marker genes (SOX9, LUM, DCN; RUNX2, SPARC, SPP1, ALPL); this was accompanied by stimulation of ALP activity (+38%±12 standard error of mean, P<0.05). Matrix analysis revealed that the osteo-chondrogenic response followed a coordinated expression pattern, in which FOS was attributed to early osteogenic but not chondrogenic differentiation.ConclusionUndifferentiated hMSCs are highly sensitive to mechanical strain with a transcriptionally controlled osteo-chondrogenic differentiation response in vitro

Matrix-associated autologous chondrocyte transplantation in a compartmentalized early stage of osteoarthritis

SummaryObjectiveCartilage restoration in joints with an early stage of osteoarthritis (OA) is an important clinical challenge. In this study, a compartmentalized, early-stage OA was generated surgically in sheep stifle joints, and this model was used to evaluate a matrix-associated cell transplantation approach for cartilage repair.MethodEighteen sheep were operated twice. During the first operation, a unicompartmental OA in a stable joint was induced by creating a critical-size defect. The second operation served as a regeneration procedure. The eighteen sheep were divided into three groups. One group was treated with spongialization (SPONGIO), while the two others had spongialization followed by implantation of a hyaluronan matrix with (MACT) or without chondrocytes (MATRIX). The follow-up took place 4 months after the second operation. Gross Assessment of Joint Changes score and Brittberg score were used for the macroscopic evaluation, Mankin score, O'Driscoll score, and immunohistochemistry for collagen type I and type II for histological evaluation.ResultsThe MACT group achieved significantly better results in both macroscopic and histological examinations. In the regeneration area, a Mankin score of 7.88 (6.20; 9.55) [mean (upper 95% confidence interval; lower 95% confidence interval)] was reached in the MACT group, 10.38 (8.03; 12.72) in the MATRIX group, and 10.33 (8.80; 11.87) in the SPONGIO group. The O'Driscoll score revealed a highly significant difference in the degree of defect repair: 15.92 (14.58; 17.25) for the MACT group compared to the two other groups [5.04 (1.21; 8.87) MATRIX and 6.58 (5.17; 8.00) SPONGIO; P < 0.0001].ConclusionThis study demonstrates promising results toward the development of a biological regeneration technique for early-stage OA

Cartilage repair of the ankle: first results of T2 mapping at 7.0 T after microfracture and matrix associated autologous cartilage transplantation

SummaryBackgroundBoth microfracture (MFX) and matrix associated autologous cartilage transplantation (MACT) are currently used to treat cartilage defects of the talus. T2 mapping of the ankle at 7 T has the potential to assess the collagen fibril network organization of the native hyaline cartilage and of the repair tissue (RT). This study provides first results regarding the properties of cartilage RT after MFX (mean follow-up: 113.8 months) and MACT (65.4 months).MethodsA multi-echo spin-echo sequence was used at 7 T to assess T2 maps in 10 volunteer cases, and in 10 cases after MFX and MACT each. Proton weighted morphological images and clinical data were used to ensure comparable baseline criteria.ResultsA significant zonal variation of T2 was found in the volunteers. T2 of the superficial and the deep layer was 39.3 ± 5.9 ms and 21.1 ± 3.1 ms (zonal T2 index calculated by superficial T2/deep T2: 1.87 ± 0.2, P < 0.001). In MFX, T2 of the reference cartilage was 37.4 ± 5.0 ms and 25.3 ± 3.5 ms (1.51 ± 0.3, P < 0.001). In the RT, T2 was 43.4 ± 10.5 ms and 36.3 ± 7.7 ms (1.20 ± 0.2, P = 0.009). In MACT, T2 of the reference cartilage was 39.0 ± 9.1 ms and 27.1 ± 6.6 ms (1.45 ± 0.2, P < 0.001). In the RT, T2 was 44.6 ± 10.4 ms and 38.6 ± 7.3 ms (1.15 ± 0.1, P = 0.003). The zonal RT T2 variation differed significantly from the reference cartilage in both techniques (MFX: P = 0.004, MACT: P = 0.001).ConclusionT2 mapping at 7 T allows for the quantitative assessment of the collagen network organization of the talus. MACT and MFX yielded RT with comparable T2 properties

Osteosarcoma of the mobile spine†

Background The aims of this analysis were to investigate features and outcome of high-grade osteosarcomas of the mobile spine. Patients and methods Since 1977, 20 Cooperative Osteosarcoma Study Group patients had a diagnosis of high-grade osteosarcomas of the mobile spine and were included in this retrospective analysis of patient-, tumor- and treatment-related variables and outcome. Results The median age was 29 years (range 5-58). Most frequent tumor sites were thoracic and lumbar spine. All but three patients had nonmetastatic disease at diagnosis. Treatment included surgery and chemotherapy for all patients, 13 were also irradiated. Eight patients failed to achieve a macroscopically complete surgical remission (five local, one primary metastases, two both), six died, two are alive, both with radiotherapy. Of 12 patients with complete remission at all sites, three had a recurrence (two local, one metastases) and died. The median follow-up of the 11 survivors was 8.7 years (range 3.1-22.3), 5-year overall and event-free survival rates were 60% and 43%. Age <40 years, nonmetastatic disease at diagnosis and complete remission predicted for better overall survival (OS, P < 0.05). Conclusions Osteosarcomas of the mobile spine are rare. With complete resection (and potentially radiotherapy) and chemotherapy, prognosis may be comparable with that of appendicular osteosarcoma

Clinical Study The Impact of Personality Traits on the Outcome of Total Knee Arthroplasty

Ten to twenty percent of patients with total knee arthroplasty (TKA) are dissatisfied with their clinical outcome. Aim of this study was to investigate the impact of personality traits on the subjective outcome of TKA. We investigated 80 patients with 86 computer navigated TKAs. We asked for patients satisfaction and divided patients into two groups (satisfied or dissatisfied). 12 personality traits were tested by the Freiburg Personality Inventory (FPI-R). Postoperative examination included Knee Society Score (KSS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and the Visual Analogue Scale (VAS). Radiologic investigation was done in all patients. 84% of our patients were satisfied, while 16% were not satisfied. The FPI-R showed statistical significant influence of four personality traits on patient satisfaction: life satisfaction ( = 0.006), performance orientation ( = 0.015), somatic distress ( = 0.001), and emotional stability ( = 0.002). All clinical scores (VAS, WOMAC, and KSS) showed significantly better results in the satisfied patient. Radiological examination showed optimal alignment of all TKAs. There were no complications requiring revision surgery. The results of our study show that personality traits may influence patients satisfaction and clinical outcome after TKA. Therefore patients personality traits may be a useful predictive factor for postoperative satisfaction after TKA

High-Grade Osteosarcoma of the Foot: Presentation, Treatment, Prognostic Factors, and Outcome of 23 Cooperative Osteosarcoma Study Group COSS Patients

Osteosarcoma of the foot is a very rare presentation of a rare tumor entity. In a retrospective analysis, we investigated tumor- and treatment-related variables and outcome of patients registered in the Cooperative Osteosarcoma Study Group (COSS) database between January 1980 and April 2016 who suffered from primary high-grade osteosarcoma of the foot. Among the 23 eligible patients, median age was 32 years (range: 6-58 years), 10 were female, and 13 were male. The tarsus was the most commonly affected site (n=16). Three patients had primary metastases. All patients were operated: 5 underwent primary surgery and 18 received surgery following preoperative chemotherapy. In 21 of the 23 patients, complete surgical remission was achieved. In 4 of 17 patients, a poor response to neoadjuvant chemotherapy was observed in the resected primary tumors. Median follow-up was 4.2 years (range: 0.4-18.5). At the last follow-up, 15 of the 23 patients were alive and 8 had died. Five-year overall and event-free survival estimates were 64% (standard error (SE) 12%) and 54% (SE 13%), which is similar to that observed for osteosarcoma in general. Event-free and overall survival correlated with primary metastatic status and completeness of surgery. Our findings show that high-grade osteosarcoma in the foot has a similar outcome as osteosarcoma of other sites

Extraskeletal osteosarcoma: A European Musculoskeletal Oncology Society study on 266 patients

PURPOSE: Prognosis of extraskeletal osteosarcoma (ESOS) is reported to be poorer than that of skeletal osteosarcoma. This multicenter retrospective study aimed to evaluate factors influencing ESOS prognosis. PATIENTS AND METHODS: Members of the European Musculoskeletal Oncology Society (EMSOS) submitted institutional data on patients with ESOS. RESULTS: Data from 274 patients treated from 1981 to 2014 were collected from 16 EMSOS centres; 266 patients were eligible. Fifty (18.7%) had metastases at diagnosis. Of 216 patients with localised disease, 211 (98%) underwent surgery (R0 = 70.6%, R1 = 27%). Five-year overall survival (OS) for all 266 patients was 47% (95% CI 40-54%). Five-year OS for metastatic patients was 27% (95% CI 13-41%). In the analysis restricted to the 211 localised patients who achieved complete remission after surgery 5-year OS was 51.4% (95% CI 44-59%) and 5-year disease-free survival (DFS) was 43% (95% CI 35-51%). One hundred twenty-one patients (57.3%) received adjuvant or neoadjuvant chemotherapy and 80 patients (37.9%) received radiotherapy. A favourable trend was seen for osteosarcoma-type chemotherapy versus soft tissue sarcoma-type (doxorubicin ± ifosfamide) regimens. For the 211 patients in complete remission after surgery, patient age, tumour size, margins and chemotherapy were positive prognostic factors for DFS and OS by univariate analysis. At multivariate analysis, patient age (≤40 years versus >40 years) (P = 0.05), tumour size (P = 0.0001) and receipt of chemotherapy (P = 0.006) were statistically significant prognostic factors for survival. CONCLUSION: Patient age and tumour size are factors influencing ESOS prognosis. Higher survival was observed in patients who received perioperative chemotherapy with a trend in favour of multiagent osteosarcoma-type regimen which included doxorubicin, ifosfamide and cisplatin.info:eu-repo/semantics/publishedVersio

Mesenchymal chondrosarcoma: prognostic factors and outcome in 113 patients. A European Musculoskeletal Oncology Society study

BACKGROUND: Mesenchymal chondrosarcoma (MCS) is a distinct, very rare sarcoma with little evidence supporting treatment recommendations. PATIENTS AND METHODS: Specialist centres collaborated to report prognostic factors and outcome for 113 patients. RESULTS: Median age was 30 years (range: 11-80), male/female ratio 1.1. Primary sites were extremities (40%), trunk (47%) and head and neck (13%), 41 arising primarily in soft tissue. Seventeen patients had metastases at diagnosis. Mean follow-up was 14.9 years (range: 1-34), median overall survival (OS) 17 years (95% confidence interval (CI): 10.3-28.6). Ninety-five of 96 patients with localised disease underwent surgery, 54 additionally received combination chemotherapy. Sixty-five of 95 patients are alive and 45 progression-free (5 local recurrence, 34 distant metastases, 11 combined). Median progression-free survival (PFS) and OS were 7 (95% CI: 3.03-10.96) and 20 (95% CI: 12.63-27.36) years respectively. Chemotherapy administration in patients with localised disease was associated with reduced risk of recurrence (P=0.046; hazard ratio (HR)=0.482 95% CI: 0.213-0.996) and death (P=0.004; HR=0.445 95% CI: 0.256-0.774). Clear resection margins predicted less frequent local recurrence (2% versus 27%; P=0.002). Primary site and origin did not influence survival. The absence of metastases at diagnosis was associated with a significantly better outcome (P<0.0001). Data on radiotherapy indications, dose and fractionation were insufficiently complete, to allow comment of its impact on outcomes. Median OS for patients with metastases at presentation was 3 years (95% CI: 0-4.25). CONCLUSIONS: Prognosis in MCS varies considerably. Metastatic disease at diagnosis has the strongest impact on survival. Complete resection and adjuvant chemotherapy should be considered as standard of care for localised disease

Clinical and functional outcomes of the saddle prosthesis

BACKGROUND:The implantation of a saddle prosthesis after resection of a pelvic tumor has been proposed as a simple method of reconstruction that provides good stability and reduces the surgical time, thus limits the onset of intraoperative complications. There are no studies in the literature of patients evaluated using gait analysis after being implanted with a saddle prosthesis. The present study is a retrospective case review aimed at illustrating long-term clinical and functional findings in tumor patients reconstructed with a saddle prosthesis. MATERIALS AND METHODS:A series of 15 patients who received pelvic reconstruction with a saddle prosthesis were retrospectively reviewed in terms of clinical, radiographic, and functional evaluations. Two patients were additionally assessed by gait analysis. RESULTS:Long-term functional follow-up was achieved in only 6 patients, and ranged from 97 to 167 months. Function was found to be rather impaired, as a mean of only 57 % of normal activity was restored. Gait analysis demonstrated that the implant had poor biomechanics, as characterized by very limited hip motion. CONCLUSIONS: Though the saddle prosthesis was proposed as advance in tumor-related pelvic surgery, the present study indicates that it yields unsatisfactory clinical and functional results due to both clinical complications and the poor biomechanics of the device. The use of a saddle prosthesis in tumor surgery did not provide satisfactory results in long-term follow-up. It is no longer implanted at our institute, and is currently considered a "salvage technique.