hondrocyte-based tissue engineering methods, including cell transplantation alone or within a scaffold, are emerging therapies for articular cartilage repair. One hypothesized mechanism for repair is that transplanted chondrocytes are retained within the defect, synthesize and deposit cartilaginous matrix to fill the defect, and integrate the newly-formed tissue with surrounding host tissue. The overall objective of this research is to provide an improved understanding of chondrocyte adhesion and matrix metabolism following transplantation to cartilage.
Receptor mediated adhesion to the surrounding cartilage extracellular matrix may provide an initial mechanism to stabilize transplanted chondrocytes within the defect. The adhesion of transplanted chondrocytes to surrounding host cartilage may be mediated by receptors including integrins, CD44, and annexin V. Rapid screening and shear flow adhesion assays were developed to quantify and characterize adhesion of bovine and human chondrocytes to cartilage in a transplantation-type procedure. Adhesion to cartilage was mediated by β1-integrins, specifically α5β1, and αvβ5. CD44, annexin V αl-, α3-, and αvβ3-integrins did not function to mediate firm attachment, even though these receptors were present on the cell surface. Delineation of the mechanisms of adhesion may have clinical implications by allowing cell manipulations or matrix treatments to enhance chondrocyte adhesion, retention and subsequent function.
In chondrocyte transplantation procedures, the metabolism of chondrocytes at the host cartilage interface may be particularly important for cartilage repair. Culture of chondrocytes in alginate gels allows recovery of cells with an associated matrix which may foster retention of newly synthesized matrix. Using an in vitro model of chondrocyte transplantation, the effect of cell-substrate interactions and a cell-associated matrix on the synthesis, deposition, and release of matrix was investigated. The substrate onto which the chondrocytes were transplanted had a significant effect on metabolism, with cells on cartilage synthesizing and retaining less glycosaminoglycan and protein than cells on tissue culture plastic. In general, chondrocytes recovered from alginate culture synthesized more glycosaminoglycan and protein following transplantation than did monolayer cultured chondrocytes. These patterns of matrix metabolism by transplanted cells have implications for repair. Regulation of chondrocyte function with culture conditions and matrix interactions may be useful for cartilage tissue engineering.
|1993||Shapiro F, Koide S, Glimcher MJ. Cell origin and differentiation in the repair of full-thickness defects of articular cartilage. J Bone Joint Surg. April 1993;75A(4):532-553.|
|1988||Aydelotte MB, Greenhill RR, Kuettner KE. Differences between sub-populations of cultured bovine articular chondrocytes, II: proteoglycan metabolism. Connect Tissue Res. 1988;18(3):223-234.|
|1982||Benya PD, Shaffer JD. Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell. August 1982;30(1):215-224.|
|1989||Sah RL-Y, Kim Y-J, Doong J-YH, Grodzinsky AJ, Plass AHK, Sandy JD. Biosynthetic response of cartilage explants to dynamic compression. J Orthop Res. 1989;7(5):619-636.|
|1982||Mankin HJ. The response of articular cartilage to mechanical injury. J Bone Joint Surg. March 1982;64A(3):460-466.|
|1985||Frangos JA, Eskin SG, McIntire LV, Ives CL. Flow effects on prostacyclin production by cultured human endothelial cells. Science. March 22, 1985;227(4693):1477-1479.|
|1986||Farndale RW, Buttle DJ, Barrett AJ. Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. Biochim Biophys Acta. September 4, 1986;883(2):173-177.|
|1995||Reindel ES, Ayroso AM, Chen AC, Chun DM, Schinagl RM, Sah RL. Integrative repair of articular cartilage in vitro: adhesive strength of the interface region. J Orthop Res. September 1995;13(5):751-760.|
|1988||Aydelotte MB, Kuettner KE. Differences between sub-populations of cultured bovine articular chondrocytes, I: morphology and cartilage matrix production. Connect Tissue Res. 1988;18(3):205-222.|
|1997||Buckwalter JA, Mankin HJ. Articular cartilage, I: tissue design and chondrocyte-matrix interactions. J Bone Joint Surg. April 1997;79A(4):600-611.|
|1994||Häuselmann HJ, Fernandes RJ, Mok SS, Schmid TM, Block JA, Aydelotte MB, Kuettner KE, Thonar EJ-MA. Phenotypic stability of bovine articular chondrocytes after long-term culture in alginate beads. J Cell Sci. January 1994;107(1):17-27.|
|1994||Wakitani S, Goto T, Pineda SJ, Young RG, Mansour JM, Caplan AI, Goldberg VM. Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg. April 1994;76A(4):579-592.|
|1988||Kim Y-J, Sah RLY, Doong J-YH, Grodzinsky AJ. Fluorometric assay of DNA in cartilage explants using Hoechst 33258. Anal Ciochem. October 1988;174(1):168-176.|
|1988||Poole CA, Ayad S, Schofield JR. Chondrons from articular cartilage, I: immunolocalization of type VI collagen in the pericellular capsule of isolated canine tibial chondrons. J Cell Sci. August 1988;90(4):635-643.|
|1994||Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. NEJM. October 6, 1994;331(14):889-895.|