Chondrogenic Differentiation of Adipose-Derived Adult Stem Cells by a Porous Scaffold Derived from Native Articular Cartilage Extracellular Matrix

Abstract

Adipose-derived adult stem cells (ASCs) have the ability to differentiate into a chondrogenic phenotype in response to specific environmental signals such as growth factors or artificial biomaterial scaffolds. In this study, we examined the hypothesis that a porous scaffold derived exclusively from articular cartilage can induce chondrogenesis of ASCs. Human ASCs were seeded on porous scaffolds derived from adult porcine articular cartilage and cultured in standard medium without exogenous growth factors. Chondrogenesis of ASCs seeded within the scaffold was evident by quantitative RT-PCR analysis for cartilage-specific extracellular matrix (ECM) genes. Histological and immunohistochemical examination showed abundant production of cartilage-specific ECM components-particularly, type II collagen-after 4 or 6 weeks of culture. After 6 weeks of culture, the cellular morphology in the ASC-seeded constructs resembled those in native articular cartilage tissue, with rounded cells residing in the glycosaminoglycan-rich regions of the scaffolds. Biphasic mechanical testing showed that the aggregate modulus of the ASC-seeded constructs increased over time, reaching 150 kPa by day 42, more than threefold higher than that of the unseeded controls. These results suggest that a porous scaffold derived from articular cartilage has the ability to induce chondrogenic differentiation of ASCs without exogenous growth factors, with significant synthesis and accumulation of ECM macromolecules, and the development of mechanical properties approaching those of native cartilage. These findings support the potential for a processed cartilage ECM as a biomaterial scaffold for cartilage tissue engineering. Additional in vivo evaluation is necessary to fully recognize the clinical implication of these observations.

Treatment of Glenoid Chondral Defect Using Micronized Allogeneic Cartilage Matrix Implantation

“…8 In vitro studies have shown that dehydrated, micronized allograft tissue promotes chondrogenesis. 9 Moreover, the BioCartilage technique uses the anabolic and anti-inflammatory benefits of PRP. Several trials have reported superior functional outcome and improved histologic scores when comparing PRPenhanced microfracture versus microfracture alone.…”

2010 Nicolas Andry Award: Multipotent Adult Stem Cells from Adipose Tissue for Musculoskeletal Tissue Engineering

“…In other studies, it was shown that biomaterial scaffolds created solely from native extracellular matrix tissues also can control the differentiation of ASCs [16,21]. Using a porous scaffold derived exclusively from articular cartilage, chondrogenesis of ASCs in the absence of exogenous growth factors was examined.…”

“…For example, after 4 weeks in culture, construct diffusivity decreased greater than 40% under chondrogenic conditions, and was associated with a net increase in the biosynthesis and retention of matrix macromolecules. [16] Volume…”

Cartilage fragments from osteoarthritic knee promote chondrogenesis of mesenchymal stem cells without exogenous growth factor induction

“…6,7 Recently, more and more ECM-derived scaffolds have been examined and fabricated to offer a specific environment for cartilage repair or regeneration. [8][9][10][11][12] A previous study has revealed that cartilage extract matrix can promote the chondrogenesis of embryonic stem cells. 7 This suggests that articular cartilage ECM may play an important role in guiding the chondrogenic differentiation of MSCs.…”