The ultimate aim of this study was to assess the feasibility of using human bone marrow stromal cells (BMSCs) to supplement meniscus cells for meniscus tissue engineering and regeneration. Human menisci were harvested from three patients undergoing total knee replacements. Meniscus cells were released from the menisci after collagenase treatment. BMSCs were harvested from the iliac crest of three patients and were expanded in culture until passage 2. Primary meniscus cells and BMSCs were co-cultured in vitro in three-dimensional (3D) pellet culture at three different cell-cell ratios for 3 weeks under normal (21% O2 ) or low (3% O2 ) oxygen tension in the presence of serum-free chondrogenic medium. Pure BMSCs and pure meniscus cell pellets served as control groups. The tissue generated was assessed biochemically, histochemically and by quantitative RT-PCR. Co-cultures of primary meniscus cells and BMSCs resulted in tissue with increased (1.3-1.7-fold) deposition of proteoglycan (GAG) extracellular matrix (ECM) relative to tissues derived from BMSCs or meniscus cells alone under 21% O2 . GAG matrix formation was also enhanced (1.3-1.6-fold) under 3% O2 culture conditions. Alcian blue staining of generated tissue confirmed increased deposition of GAG-rich matrix. mRNA expression of type I collagen (COL1A2), type II collagen (COL2A1) and aggrecan were upregulated in co-cultured pellets. However, SOX9 and HIF-1α mRNA expression were not significantly modulated by co-culture. Co-culture of primary meniscus cells with BMSCs resulted in increased ECM formation. Co-delivery of meniscus cells and BMSCs can, in principle, be used in tissue engineering and regenerative medicine strategies to repair meniscus defects.

BackgroundA major consequence of stroke is permanent motor disturbance, such as postural imbalance and loss of skilled movement. The degree of neuronal and functional loss and subsequent recovery after stroke is influenced by hypothalamic-pituitary-adrenal axis activation and the response to glucocorticoid hormones. This study investigated if recovery after stroke is related to glucocorticoid receptor (GR) activation in a rat model of stroke.MethodsAdult male rats were pre-trained and tested in a skilled reaching task and received a focal ischemic motor cortex lesion. One group of animals received daily restraint stress starting one week pre-lesion up to three weeks post-lesion. Immuno-histochemical analysis of GR expression was performed to determine receptor activation.ResultsStress reduced reaching success in naïve animals and diminished recovery of limb use. Exaggerated functional loss in stressed rats was related to increased GR activation in the lesion hemisphere as indicated by nuclear GR location.ConclusionThese findings provide a mechanistic link between stress-induced motor disability and GR activation in a rat model of stroke. The elevated receptor activation proposes synergistic effects of stress and stroke to modulate the impact of glucocorticoids on motor system function at the genomic level. The modulation of GR biosynthesis may alter responsiveness to stroke treatment and compromise recovery.

Background: To date, little clinical evidence exists to support a specific surgical technique or postoperative rehabilitation protocol for quadriceps tendon ruptures. With a lack of evidence-based superiority, assessment of clinical practices and surgeon preferences is pertinent. Purpose: To describe the current surgical technique and rehabilitation preferences among members of the Canadian Orthopaedic Association and American Orthopaedic Society for Sports Medicine pertaining to acute quadriceps tendon rupture. Study Design: Cross-sectional study. Methods: Orthopaedic staff members of the Canadian Orthopaedic Association and American Orthopaedic Society for Sports Medicine were invited to complete an internet-based survey composed of 26 questions assessing current trends in the management and rehabilitation of acute quadriceps tendon rupture. Survey questions were developed after a thorough review of current literature. Survey responses were analyzed and reported using descriptive statistics (absolute values, frequencies, and percentages) where appropriate. Statistical comparisons and contrasts between Canadian and American surgeons were made using chi-square analyses and Student t tests. Results: A total of 264 surgeons participated in the survey (136 Canadians; 128 Americans). Canadian surgeons were more likely to obtain a preoperative ultrasound as compared with Americans (43.0% vs 6.7%; P < .00001), while American respondents were more likely to obtain magnetic resonance imaging scans (65.8% vs 10.2%; P < .00001). The transosseous drill hole technique was the most commonly utilized (70.2%); the suture anchor technique was used 20.6% of the time. Canadian respondents trended toward a higher use of transosseous tunnels; however, this was not statistically significant (75.8% vs 64.2%; P = .068). American respondents were more likely to utilize suture anchors (27.5% vs 14.1%; P = .0096). Most respondents advanced range of motion goals stepwise in 2-week intervals of 30° (Canadians, 54.0% vs Americans, 58.5%; P = .3091); timing of range of motion initiation varied. Conclusion: Among North American surgeons who responded to this study, the transosseous technique was the most commonly used, and range of motion was generally advanced in a 2-week stepwise fashion. We found several differences in practice between Canadian and American respondents, including the type of preoperative imaging and the frequency of using the suture anchor technique.