Effect of chondroitinase ABC on adhesion and behavior of synovial membrane-derived mesenchymal stem cells in rabbit partial-thickness chondral defects
Department of Orthopedic Surgery, Seoul National University College of Medicine, #28 Yongondong, Chongnogu, Seoul, 110-744, Republic of Korea.Journal of Orthopaedic Research (Impact Factor: 2.99). 08/2013; 31(8). DOI: 10.1002/jor.22353
Transplanted cells may have difficulty attaching to the surface of partial-thickness chondral lesions because of the anti-adhesive properties of the proteoglycan rich matrix. Therefore, the current study attempts to evaluate the effect of chondroitinase ABC (chABC) on the adhesion and behavior of transplanted synovial membrane-derived mesenchymal stem cells (SDSCs) in rabbit partial-thickness chondral defects. In ex vivo adhesion experiments, chABC treatment (0.1 U/ml) was increased in SDSC attachment to the cartilage explants, and significantly diminished by pretreatment with neutralizing antibody against fibronectin. In the in vivo experiments, 1 day and 4 weeks after the chABC treatment (0.1 and 1 U/ml), the immunoreactivity (IR) against CS-56 (intact chondroitin sulfate antibody) was markedly decreased; however, the IR of 2B6 (stub of the chondroitin 4-sulfate chain), 3B3 (stub of the chondroitin 6-sulfate chain), and fibronectin was increased. At 12 weeks, this IR returned to normal except in the high-dose chABC-treated group (1 U/ml). Furthermore, the attachment of SDSCs to the chondral defects after chABC treatment was increased at 7 days compared with that in the chondral defects pretreated with saline. However, the tissue repaired by SDSCs was negatively stained for type II collagen at 12 weeks. In conclusion, these results showed that the exposure to fibronectin by chABC treatment enhances the attachment of SDSCs to partial-thickness chondral defects. However, the tissue regenerated by SDSCs showed lack of hyaline cartilage regeneration. Thus, to understand the fate of transplanted MSCs in cartilage defect is very important for successful cell therapies. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res.
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ABSTRACT: Partial thickness articular cartilage injuries (PTCIs) were not previously thought to heal spontaneously. Immature rats have the capacity for spontaneous repair of PTCIs, although it is a long-term process. Our aim has been to examine the spontaneous repair response mechanism in immature rats. Single linear PTCIs were created in 3-week-old and 12-week-old rats in the direction of joint motion. On day 1 and at 1, 2, and 4 weeks after PTCI, evaluations of histological changes and immunohistology at the injury site and in the surrounding cartilage were performed. Anti-CD105 and anti-CD166 antibodies (as stem cell markers to identify mesenchymal stem cells in reparative cartilage tissue) were used for immunohistological evaluations. To determine whether endogenous repair ability existed in articular cartilage, an ex vivo experiment was also carried out. Femoral condyles with PTCIs were incubated in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum for 1 day and for 1 and 2 weeks. Histological changes were subsequently examined. Immature cartilage showed a higher repair response than did mature cartilage, and the response occurred immediately after PTCI. In immature rats, CD105- and CD166-positive cells were found in the superficial and transitional zones of the articular cartilage. Few CD166-positive cells were identified in mature articular cartilage. No significant in vivo differences in the spontaneous repair responses to PTCIs were observed between mature and immature groups. Thus, the repair response to PTCIs seems to be associated not only with CD105- and CD166-positive cells, but also with other perichondral factors.Cell and Tissue Research 11/2014; 359(2). DOI:10.1007/s00441-014-2041-3 · 3.57 Impact Factor
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ABSTRACT: Transplantation of mesenchymal stromal cells (MSCs) has been identified as a potential therapeutic modality for treating spinal cord injury (SCI). Degradation of chondroitin sulfate proteoglycans (CSPGs) using the enzyme chondroitinase ABC (chABC) can promote functional recovery after SCI. The effect of the simultaneous administration of MSCs and chABC on chronic SCI was investigated. Sixteen dogs were assigned to one of the following four groups: (i) canine adipose tissue-derived MSCs (cADMSCs), (ii) chABC, (iii) cADMSCs + chABC and (iv) control. Treatments were carried out 3 weeks after SCI; cADMSCs (1 × 10(7) cells suspended in 150 μL of PBS), chABC (5 U/mL, 150 μL), cADMSCs + chABC (1 × 10(7) cells suspended in 150 μL of chABC), or phosphate-buffered saline (150 μL) were injected into the spinal cord at three locations to a depth of 3 mm using a 30-gauge needle. The spinal cord was harvested 8 weeks after transplantation. In a behavioral assessment, dogs treated with cADMSCs + chABC and cADMSCs alone showed significantly better functional recovery 8 weeks after transplantation compared with the control and chABC groups (P < 0.05). In addition, the combination of cADMSCs and chABC increased the expression of digested CSPGs (2B6), β3 tubulin, and NF-M. However, the levels of COX2 (P < 0.05), and tumor necrosis factor-α was higher in the treatment groups than in the control. In conclusion, transplantation of cADMSCs + chABC was more effective in improving clinical signs and neural regeneration, but a strategy for anti-inflammation after the treatment for chronic SCI would be needed for further improvement. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.Cytotherapy 07/2015; 17(10). DOI:10.1016/j.jcyt.2015.05.012 · 3.29 Impact Factor
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