The Challenge in Using Mesenchymal Stromal Cells for Recellularization of Decellularized Cartilage

Abstract

Some decellularized musculoskeletal extracellular matrices (ECM)s derived from tissues such as bone, tendon and fibrocartilaginous meniscus have already been clinical use for tissue reconstruction. Repair of articular cartilage with its unique zonal ECM architecture and composition is still an unsolved problem, and the question is whether allogenic or xenogeneic decellularized cartilage ECM could serve as a biomimetic scaffold for this purpose.Hence, this survey outlines the present state of preparing decellularized cartilage ECM-derived scaffolds or composites for reconstruction of different cartilage types and of reseeding it particularly with mesenchymal stromal cells (MSCs).The preparation of natural decellularized cartilage ECM scaffolds hampers from the high density of the cartilage ECM and lacking interconnectivity of the rather small natural pores within it: the chondrocytes lacunae. Nevertheless, the reseeding of decellularized ECM scaffolds before implantation provided superior results compared with simply implanting cell-free constructs in several other tissues, but cartilage recellularization remains still challenging. Induced by cartilage ECM-derived scaffolds MSCs underwent chondrogenesis.Major problems to be addressed for the application of cell-free cartilage were discussed such as to maintain ECM structure, natural chemistry, biomechanics and to achieve a homogenous and stable cell recolonization, promote chondrogenic and prevent terminal differentiation (hypertrophy) and induce the deposition of a novel functional ECM. Some promising approaches were proposed including further processing of the decellularized ECM before recellularization of the ECM with MSCs, co-culturing of MSCs with chondrocytes and establishing bioreactor culture e.g. with mechanostimulation, flow perfusion pressure and lowered oxygen tension. Graphical Abstract Synopsis of tissue engineering approaches based on cartilage-derived ECM.

Osteochondritis dissecans (OCD) in Horses – Molecular Background of its Pathogenesis and Perspectives for Progenitor Stem Cell Therapy

“…[ 34 ]. Indeed, the cartilaginous tissue is characterized by a simplified structuring, comprising only one cell type (chondrocytes) and an abundant ECM with high content of fibrous proteins (mainly type II collagen) and water-binding, mostly sulfated glycosaminoglycans (sGAG) [ 35 ]. However, articular cartilage development is orchestrated by a cascade of molecular events regulated by various growth factors whose interactions allow the establishment of a well-designed architecture [ 34 ].…”

Carrageenan enhances chondrogenesis and osteogenesis in human bone marrow stem cell culture

“…Decellularised stem, permanently differentiated and immortalised cell-derived matrices are traditionally used to either support efficient stem cell expansion or to direct stem cells towards a specific lineage (Cheng et al, 2014;Fitzpatrick and McDevitt, 2015;Harris et al, 2018;Kaukonen et al, 2017;Kusuma et al, 2017). However, again due to slow and low level of ECM deposition in traditional in vitro systems, among others, cell-ECM interactions and interconnectivity are not mimicked, leading to less and often uncontrollable differentiation/unwanted trans-differentiation (Choi et al, 2012;Huang et al, 2017;Kwon et al, 2013;Marinkovic et al, 2016).…”

Bio-Engineered Meniscus for Tissue Engineering

“…Drawbacks of using mesenchymal stem cells lies in the complex understanding of required stimuli to direct the differentiation process to a desired lineage [48]. Besides that, once the microenvironment changes and undergo hypertrophy, the differentiated phenotype can be easily lost [53].…”