In vivo cartilage repair using adipose-derived stem cell-loaded decellularized cartilage ECM scaffolds.
ABSTRACT We have previously reported a natural, human cartilage ECM (extracellular matrix)-derived three-dimensional (3D) porous acellular scaffold for in vivo cartilage tissue engineering in nude mice. However, the in vivo repair effects of this scaffold are still unknown. The aim of this study was to further explore the feasibility of application of cell-loaded scaffolds, using autologous adipose-derived stem cells (ADSCs), for cartilage defect repair in rabbits. A defect 4 mm in diameter was created on the patellar groove of the femur in both knees, and was repaired with the chondrogenically induced ADSC-scaffold constructs (group A) or the scaffold alone (group B); defects without treatment were used as controls (group C). The results showed that in group A all defects were fully filled with repair tissue and at 6 months post-surgery most of the repair site was filled with hyaline cartilage. In contrast, in group B all defects were partially filled with repair tissue, but only half of the repair tissue was hyaline cartilage. Defects were only filled with fibrotic tissue in group C. Indeed, histological grading score analysis revealed that an average score in group A was higher than in groups B and C. GAG and type II collagen content and biomechanical property detection showed that the group A levels approached those of normal cartilage. In conclusion, ADSC-loaded cartilage ECM scaffolds induced cartilage repair tissue comparable to native cartilage in terms of mechanical properties and biochemical components. Copyright © 2012 John Wiley & Sons, Ltd.
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ABSTRACT: Osteochondral interface regeneration is challenging for functional and integrated cartilage repair. Various layered scaffolds have been used to reconstruct the complex interface, yet the influence of the permeability of the layered structure on cartilage defect healing remains largely unknown.BioMedical Engineering OnLine 06/2014; 13(1):80. DOI:10.1186/1475-925X-13-80 · 1.75 Impact Factor
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ABSTRACT: Cell-based therapies have recently been proposed for the treatment of degenerative articular pathologies, such as early osteoarthritis, with an emphasis on autologous mesenchymal stem cells (MSCs), as an alternative to terminally differentiated cells. In this study, we performed a donor-matched comparison between infrapatellar fat pad MSCs (IFP-MSCs) and knee subcutaneous adipose tissue stem cells (ASCs), as appealing candidates for cell-based therapies that are easily accessible during surgery. IFP-MSCs and ASCs were obtained from 25 osteoarthritic patients undergoing total knee replacement and compared for their immunophenotype and differentiative potential. Undifferentiated IFP-MSCs and ASCs displayed the same immunophenotype, typical of MSCs (CD13+/CD29+/CD44+/CD73+/CD90+/CD105+/CD166+/CD31-/CD45-). IFP-MSCs and ASCs showed similar adipogenic potential, though undifferentiated ASCs had higher LEP expression compared to IFP-MSCs (p < 0.01). Higher levels of calcified matrix (p < 0.05) and alkaline phosphatase (p < 0.05) in ASCs highlighted their superior osteogenic commitment compared to IFP-MSCs. Conversely, IFP-MSCs pellets showed greater amounts of glycosaminoglycans (p < 0.01) and superior expression of ACAN (p < 0.001), SOX9, COMP (p < 0.001) and COL2A1 (p < 0.05) compared to ASCs pellets, revealing a superior chondrogenic potential. This was also supported by lower COL10A1 (p < 0.05) and COL1A1 (p < 0.01) expression and lower alkaline phosphatase release (p < 0.05) by IFP-MSCs compared to ASCs. The observed dissimilarities between IFP-MSCs and ASCs show that, despite expressing similar surface markers, MSCs deriving from different fat depots in the same surgical site possess specific features. Furthermore, the in vitro peculiar commitment of IFP-MSCs and ASCs from osteoarthritic donors towards the chondrogenic or osteogenic lineage may suggest a preferential use for cartilage and bone cell-based treatments, respectively.European cells & materials 01/2014; 27:298-311. · 4.89 Impact Factor
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ABSTRACT: Regenerative therapies for cartilage defects have been greatly advanced by progress in both the stem cell biology and tissue engineering fields. Despite notable successes, significant barriers remain including shortage of autologous cell sources and generation of a stable chondrocyte phenotype using progenitor cells. Increasing demands for the treatment of degenerative diseases such as osteoarthritis and rheumatoid arthritis highlight the importance of epigenetic remodeling in cartilage regeneration. Epigenetic regulatory mechanisms such as microRNAs, DNA methylation and histone modifications have been intensively studied due to their direct regulatory role on gene expression. However, a thorough understanding of the environmental factors which initiate these epigenetic events may provide greater insight into the prevention of degenerative diseases and improve the efficacy of treatments. In other words, if we could identify a specific factor from the environment and its downstream signaling events, we could stop or retard degradation and enhance cartilage regeneration. A more operational definition of epigenetic remodeling has recently been proposed by categorizing the signals during the epigenetic process into epigenators, initiators and maintainers. This review seeks to compile and reorganize the existing literature pertaining to epigenetic remodeling events placing emphasis on perceiving the landscape of epigenetic mechanisms during cartilage regeneration with the new operational definition, especially from the environmental factors' point of view. Progress in understanding epigenetic regulatory mechanisms could benefit cartilage regeneration and engineering on a larger scale and provide more promising therapeutic applications.Stem cells and development 02/2014; DOI:10.1089/scd.2014.0002 · 4.15 Impact Factor