Three-Dimensional Cell Expansion Substrate for Cartilage Tissue Engineering and Regeneration: A Comparison in Decellularized Matrix Deposited by Synovium-Derived Stem Cells and Chondrocytes

Abstract

Objectives: Synovium-derived stem cells (SDSCs) are tissue-specific stem cells for chondrogenesis. Our aim was to evaluate whether decellularized matrix deposited by SDSCs was superior to chondrocytes in providing a stem cell microenvironment to conduct large scale expansion of high-quality cells for cartilage tissue engineering. Materials and Methods: We generated two extracellular matrices (ECMs) deposited by either SDSCs (SECM) or chondrocytes (CECM). Passage 4 SDSCs and chondrocytes were expanded separately for two passages on three substrates: conventional plastic flasks (Plastic), SECM, or CECM. Expanded cells were incubated in a pellet culture system supplemented with serum-free chondrogenic medium for 14 days. Histology, biochemistry, real-time PCR, and western blot were used to evaluate expanded cell chondrogenic capacity. Results: Cell proliferation was greatly improved during expansion on both ECMs, especially on SECM. ECM expansion enhanced cell chondrogenic potential, particularly for cells expanded on SECM. Collagen II and aggrecan were deposited only in CECM while collagen I and decorin existed in both ECMs. High levels of phospho-TGF-β receptor II found in chondrogenically induced cells after expansion on either ECM suggested that enhancement of chondrogenic potential might result from upregulated sensitivity in ECM-expanded cells when they are chondrogenically induced. Conclusions: SECM is superior to CECM in promoting cell expansion and enhancing expanded cell chondrogenic potential. Decellularized stem cell matrix can serve as a novel cell expansion system for cartilage tissue engineering.