Stem Cells from New Sources for Cartilage Tissue Engineering

Abstract

Problem The use of adult mesenchymal stem cells (MSC) – especially from new sources including adipose tissue - offers new perspectives in the generation of transplants for reconstructive surgery. The extracellular matrix (ECM) plays a key role in modulating function and phenotype of the embedded cells and contains the integrins as adhesion receptors mediating cell-cell- and cell-matrix-interactions. In our study, characteristic changes in integrin expression during the course of chondrogenic differentiation of MSC from bone marrow and adipose tissue were compared. Methods MSC were isolated from bone marrow biopsies and adipose tissue. During cell culture, chondrogenic differentiation was performed. The expression of Integrins and their signaling components were analyzed with microarray and immunohistochemistry in freshly isolated MSC and after chondrogenic differentiation. Results The Fibronectin-Receptor (Integrin a5b1) was expressed by undifferentiated MSC, expression rose during chondrogenic differentiation in both types of MSC. The components of the Vitronectin/Osteopontin-Receptors (avb5) were not expressed by freshly isolated MSC. Expression rose with ongoing differentiation. Receptors for Collagens (a1b1, a2b1, a3b1) were weakly expressed by undifferentiated MSC and were activated during differentiation. As intracellular signaling components integrin linked kinase (ILK) and CD47 showed increasing expression with ongoing differentiation. For all integrins, no significant differences could be found in the 2 types of MSC. Conclusion Integrin-mediated signaling seems to play an important role in the generation and maintenance of the chondrocytic phenotype during chondrogenic differentiation. The receptors for Fibronectin, Vitronectin, Osteopontin and Collagens in particular might be involved in the generation of the ECM. Intracellularly, their signals might be transduced by ILK and CD47. Significance To fully harness the potential of these cells, future studies should be directed to ascertain their cellular and molecular characteristics for optimal identification, isolation, and expansion.