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    • 2015-10-06

    Administering human adipose-derived mesenchymal stem cells to prevent and treat experimental arthritis.

    요약 : 
    Rheumatoid arthritis is a chronic autoimmune disease and affecting approximately 1% of the population. Human adipose-derived mesenchymal stem cells (hASCs) were recently found to suppress effector T cell and inflammatory responses and, thus, to have beneficial effects in various autoimmune diseases. In this study, we examined whether hASCs could play a protective and/or therapeutic role in collagen-induced arthritis (CIA). We showed that hASCs both prevented and treated CIA by significantly reducing the incidence and severity of experimental arthritis. We further demonstrated that treatment with hASCs inhibited the production of various inflammatory mediators, decreased antigen-specific Th1/Th17 cell expansion, and induced the production of anti-inflammatory cytokine interleukin-10. Moreover, hASCs could induce the generation of antigen-specific Treg cells with the capacity to suppress collagen-specific T cell responses.

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    • 2015-10-06

    Establishment of efficacy and safety assessment of human adipose tissue-derived mesenchymal stem cells (hATMSCs) in a nude rat femoral segmental defect model

    요약 : 
    Human adipose tissue-derived mesenchymal stem cell (hATMSC) have emerged as a potentially powerful tool for bone repair, but an appropriate evaluation system has not been established. The purpose of this study was to establish a preclinical assessment system to evaluate the efficacy and safety of cell therapies in a nude rat bone defect model. Segmental defects (5 mm) were created in the femoral diaphyses and transplanted with
    cell media (control), hydroxyapatite/tricalcium phosphate scaffolds (HA/TCP, Group I), hATMSCs (Group II), or three cell-loading density of hATMSC-loaded HA/TCP (Group III-V). Healing response was evaluated by serial radiography, micro-computed tomography and histology at 16 weeks. To address safety-concerns, we conducted a GLP-compliant toxicity study. Scanning electron microscopy studies showed that hATMSCs filled the pores/surfaces of scaffolds in a cell-loading density-dependent manner. We detected significant increases in bone formation in the hATMSC-loaded HA/TCP groups compared with other groups. The amount of new bone formation increased with increases in loaded cell number. In a toxicity study, no significant hATMSC-related changes were found in body weights, clinical signs, hematological/biochemical values, organ weights, or histopathological findings. In conclusion, hATMSCs loaded on HA/TCP enhance the repair of bone defects and was found to be safe under our preclinical efficacy/safety hybrid assessment system.

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    • 2015-10-06

    Long-term Follow-up after Implantation of Autologous Adipose Tissue Derived Mesenchymal Stem Cells to Treat a Dog with Stifle Joint Osteoarthrosis

    요약 : 
    A 5-year-old castrated male Chihuahua weighing 1.54 kg was examined because of a several month history of progressive right hind limb lameness. Physical examination of the stifle joints revealed pain and a grade IV medial patellar luxation on the right stifle joint. The right and left stifle joints were associated with a lameness of grade 2 and grade 0, respectively. Radiography revealed osteophytes or subchondral cystic lesions on the right and left stifle joints. Osteoarthrosis (OA) scores for the right and left stifle joints were 20 and 12 respectively. Combination of surgery and implantation of autologous adipose tissue derived mesenchymal stem cells (aAT-MSCs) was determined with informed consent. 1 × 106 aAT-MSCs suspended in PBS and 0.6 mL of hyaluronic acid were injected in the right stifle joint postoperatively. Osteoarthrosis scores and the lameness grade for the right and left stifle joints were 19 and 13, and 0 and 0 19 months after treatment, respectively, and 14 and 15, and 0 and 0 five years after treatment, respectively. This case report shows radiographical evidence of a decrease in osteophytes and subchondral cystic lesions on the stifle joint with OA after aAT-MSCs injection.

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    • 2015-10-06

    Intra-articular Injection of Mesenchymal Stem Cells for the Treatment of Osteoarthritis of the Knee: A Proof-of-Concept Clinical Trial

    요약 :
    Mesenchymal stem cells (MSCs) are known to have a potential for articular cartilage regeneration. However, most studies focused on focal cartilage defect through surgical implantation. For the treatment of generalized cartilage loss in osteoarthritis, an alternative delivery strategy would be more appropriate. The purpose of this study was to assess the safety and efficacy of intra-articular injection of autologous adipose tissue derived MSCs (AD-MSCs) for knee osteoarthritis. We enrolled 18 patients with osteoarthritis of the knee and injected AD MSCs into the knee. The phase I study consists of three dose-escalation cohorts; the low-dose (1.0 3 107 cells), mid-dose (5.0 3 107), and high-dose (1.0 3 108) group with three patients each. The phase II included nine patients receiving the high-dose. The primary outcomes were the safety and the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) at 6 months. Secondary outcomes included clinical, radiological, arthroscopic, and histological evaluations. There was no treatment-related adverse event.
    The WOMAC score improved at 6 months after injection in the high-dose group. The size of cartilage defect decreased while the volume of cartilage increased in the medial femoral and tibial condyles of the high-dose group. Arthroscopy showed that the size of cartilage defect decreased in the medial femoral and medial tibial condyles of the high-dose group. Histology demonstrated thick, hyaline-like cartilage regeneration. These results showed that intra-articular injection of 1.0 3 108 AD MSCs into the osteoarthritic knee improved function and pain of the knee joint without causing adverse events, and reduced cartilage defects by regeneration of hyaline-like articular cartilage

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