β1 Integrins Mediate Attachment of Mesenchymal Stem Cells to Cartilage Lesions
نویسندگان
چکیده
Mesenchymal stem cells (MSC) may have great potential for cell-based therapies of osteoarthritis. However, after injection in the joint, only few cells adhere to defective articular cartilage and contribute to cartilage regeneration. Little is known about the molecular mechanisms of MSC attachment to defective articular cartilage. Here, we developed an ex vivo attachment system, using rat osteochondral explants with artificially created full-thickness cartilage defects in combination with genetically labeled MSC isolated from bone marrow of human placental alkaline phosphatase transgenic rats. Binding of MSC to full-thickness cartilage lesions was improved by serum, but not hyaluronic acid, and was dependent on the presence of divalent cations. Additional in vitro tests showed that rat MSC attach, in a divalent cation-dependent manner, to collagen I, collagen II, and fibronectin, but not to collagen XXII or cartilage oligomeric matrix protein (COMP). RGD peptides partially blocked the adhesion of MSC to fibronectin in vitro and to cartilage lesions ex vivo. Furthermore, the attachment of MSC to collagen I and II in vitro and to cartilage lesions ex vivo was almost completely abolished in the presence of a β1 integrin blocking antibody. In conclusion, our data suggest that attachment of MSC to ex vivo full-thickness cartilage lesions is almost entirely β1 integrin-mediated, whereby both RGD- and collagen-binding integrins are involved. These findings suggest a key role of integrins during MSC attachment to defective cartilage and may pave the way for improved MSC-based therapies in the future.
منابع مشابه
Improvement of Expression of α6 and β1 Integrins by the Co-culture of Adult Mouse Spermatogonial Stem Cells with SIM Mouse Embryonic Fibroblast Cells (STO) and Growth Factors
متن کامل
Magnesium enhances adherence and cartilage formation of synovial mesenchymal stem cells through integrins.
OBJECTIVE We previously reported that more than 60% of synovial mesenchymal stem cells (MSCs) placed on osteochondral defects adhered to the defect within 10 min and promoted cartilage regeneration. The efficiency of adherence is considered to depend on the interaction between cells and extracellular matrix (ECM), in which integrins may play some important roles. Divalent cations such as calciu...
متن کاملMale germ-like cell differentiation potential of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells in co-culture with human placenta cells in presence of BMP4 and retinoic acid
Objective(s):Mesenchymal stem cells (MSCs) derived from Wharton’s jelly (WJ-MSCs) are now much more appealing for cell-based infertility therapy. Hence, WJ-MSCs differentiation toward germ layer cells for cell therapy purposes is currently under intensive study. Materials and Methods: MSCs were isolated from human Wharton’s jelly and treated with BMP4, retinoic acid (RA) or co-cultured on huma...
متن کاملTGF-Β1 Transduced Mesenchymal Stem Cells Have Profound Modulatory Effects on DCs and T Cells
Background: Mesenchymal stem cells (MSCs) and transforming growth factor-β1 (TGF-β1) molecules are well known for their immunomodulatory properties and their function in tissue regeneration and remodeling. Objectives: To evaluate the interaction of TGF-β1 engineered MSCs with T cells and dendritic cells (DCs) and their modulatory effect on the immune response. Methods: MSCs and DCs were generat...
متن کاملMesenchymal Stem Cell Purification from the Articular Cartilage Cell Culture
Objective Articular cartilage as an avascular skeletal tissue possesses limited capacity to heal. On the other hand, it is believed that the regeneration capacity of each tissue is largely related to its stem cell contents. Little is known about the presence of mesenchymal stem cells in articular cartilage tissue. This subject is investigated in the present study. Materials and Methods Artic...
متن کامل