Scaling up human mesenchymal stem cell manufacturing using bioreactors for clinical uses.

Human mesenchymal stem cells (hMSCs) are multipotent cells and an attractive therapeutic agent in regenerative medicine and intensive clinical research. Despite the great potential, the limitation that needs to be overcome is the necessity of ex vivo expansion because of insufficient number of hMSCs presented within adult organs and the high doses required for a transplantation. As a result, numerous research studies aim to provide novel expansion methods in order to achieve appropriate numbers of cells with preserved therapeutic quality. Bioreactor-based cell expansion provide high-level production of hMSCs in accordance with good manufacturing practice (GMP) and quality standards. This review summarizes current knowledge about the hMSCs manufacturing platforms with a main focus to the application of bioreactors for large-scale production of GMP-grade hMSCs.

Effects of Combined Allogenic Adipose Stem Cells and Hyperbaric Oxygenation Treatment on Pathogenesis of Osteoarthritis in Knee Joint Induced by Monoiodoacetate.

The beneficial effects of HBO in inflammatory processes make it an attractive type of treatment for chronic arthritis. In addition, the effects of combination therapy based on adipose stem cells and HBO on OA progression have not been fully investigated. The current study explored the efficacy of intra-articular injection of allogeneic adipose-derived mesenchymal stem cells (ADMSCs) combined with hyperbaric oxygenation treatment (HBO) in a rat osteoarthritis (OA) model. The rat OA model was induced by intra-articular injection of monoiodoacetate (MIA) and 7 days after application of MIA rats were divided into five groups: healthy control (CTRL), osteoarthritis (OA), ADMSCs (ADS), the HBO+ADS21day and HBO+ADS28day groups. A single dose of 1 × 106 allogeneic ADMSCs suspended in sterile saline was injected into the knee joint alone or in combination with HBO treatment. Rats were sacrificed at 3 or 4 weeks after MIA injection. Treatment outcomes were evaluated by radiographic, morphological and histological analysis and by specific staining of articular cartilage. We also measured the level of inflammatory and pro/antioxidative markers. We confirmed that combined treatment of ADMSCs and HBO significantly improved the regeneration of cartilage in the knee joint. Rtg score of knee joint damage was significantly decreased in the HBO+ADS21day and HBO+ADS28day groups compared to the OA. However, the positive effect in the HBO+ADS28day group was greater than the HBO+ADS21day group. The articular cartilage was relatively normal in the HBO+ADS28day group, but moderate degeneration was observed in the HBO+ADS21day compared to the OA group. These findings are in line with the histopathological results. A significantly lower level of O2-. was observed in the HBO+ADS28day group but a higher NO level compared to the HBO+ADS21day group. Moreover, in the HBO+ADS28day group significantly higher concentrations of IL-10 were observed but there was no significant difference in proinflammatory cytokine in serum samples. These results indicate that a single intra-articular injection of allogeneic ADMSCs combined with HBO efficiently attenuated OA progression after 28 days with greater therapeutic effect compared to alone ADMSCs or after 3 weeks of combined treatment. Combined treatment might be an effective treatment for OA in humans.

[Operative vs. non-operative treatment of acute Achilles tendon rupture].

INTRODUCTION: It affects most frequently middle aged recreational male sportsmen (30-50 years old), previously followed by prodromal symptoms (5-33%). Rupture spot is 3 to 5 cm above heel bone vertex (90-95%) Retrospective study. WORKING OBJECTIVE: Comparison of functional re-. suits and complications of cast immobilization non-operative treatment and open suture surgical treatment. MATERIAL AND METHODS: Overall 46 patients included who were treated at the Clinic for Orthopedics and Traumatology within the Clinical Center of Montenegro in Podgorica between 2004 and 2012. Patients were divided into two groups: I group consisted of 21 patients (45.65%) who were treated by cast immobilization and the II (control) group consisted of 25 patients (54.35%) who were treated by open surgical technique. Division by gender: 44 male patients (95.65%) and 2 female patients (4.35%). WORKING RESULTS: The average age of patients was 38.8 +/- 2.79 (21-60 years of age); for the patients treated operationally 37.1 +/- 3.98 years of age, for the patients treated non-operationally 40.2 +/- 2.39; 28 right side patients (60.86%), 18 left side patients (39.14%); Surface infection detected on 1 patient (2.17%); 2 patients with partial rupture, while 3 patients had complete rupture during early rehabilitation period after immobilization was taken off. Complete rupture detected on 3 patients (6.25%) has been recovered surgically. Thromboembolism noticed on 3 patients (6.52%) while 2 patients (4.34%) were affected by pulmonary embolism. Tendon elongation present on 3 patients (Magnetic Resonance (MR) Diagnostics) and on 1 patient reoperation was performed 3 months after the primary surgical intervention. CONCLUSION: This study didn't show significant statistical difference between two ways of treatment, but early immobilization is recommended because of better results. In case of Achilles tendon rupture, the advantage should be given to the surgical treatment, especially if younger population is treated.