Abstract:In the past 3 decades, the cartilage repair potential of mesenchymal stromal cells, or mesenchymal stem cells (MSCs), has been widely examined in animal studies. Unfortunately, the phenotype and physical properties of MSC-derived cartilage tissue are not comparable to native hyaline cartilage. In particular, chondrocytic hypertrophy, a phenotype that is not observed in healthy hyaline cartilage, is concomitant with MSC chondrogenesis. Given that hypertrophic chondrocytes potentially undergo apoptosis or conver… Show more
“…Human BM-MSCs (hBM-MSCs) cultured with a combination of Wnt3a and FGF2 supported extensive cell expansion over multiple passages and improved subsequent chondrogenic differentiation, increasing GAGs and COL2 content [ 81 ]. During late-stage chondrogenesis, active WNT signaling can promote osteogenesis [ 82 ]. Addition of the WNT inhibitor IWP2 for the last weeks of culturing reduced the content of hypertrophic and osteogenic markers in differentiating BM-MSCs [ 81 ].…”
Damaged hyaline cartilage gradually decreases joint function and growing pain significantly reduces the quality of a patient’s life. The clinically approved procedure of autologous chondrocyte implantation (ACI) for treating knee cartilage lesions has several limits, including the absence of healthy articular cartilage tissues for cell isolation and difficulties related to the chondrocyte expansion in vitro. Today, various ACI modifications are being developed using autologous chondrocytes from alternative sources, such as the auricles, nose and ribs. Adult stem cells from different tissues are also of great interest due to their less traumatic material extraction and their innate abilities of active proliferation and chondrogenic differentiation. According to the different adult stem cell types and their origin, various strategies have been proposed for stem cell expansion and initiation of their chondrogenic differentiation. The current review presents the diversity in developing applied techniques based on autologous adult stem cell differentiation to hyaline cartilage tissue and targeted to articular cartilage damage therapy.
“…Human BM-MSCs (hBM-MSCs) cultured with a combination of Wnt3a and FGF2 supported extensive cell expansion over multiple passages and improved subsequent chondrogenic differentiation, increasing GAGs and COL2 content [ 81 ]. During late-stage chondrogenesis, active WNT signaling can promote osteogenesis [ 82 ]. Addition of the WNT inhibitor IWP2 for the last weeks of culturing reduced the content of hypertrophic and osteogenic markers in differentiating BM-MSCs [ 81 ].…”
Damaged hyaline cartilage gradually decreases joint function and growing pain significantly reduces the quality of a patient’s life. The clinically approved procedure of autologous chondrocyte implantation (ACI) for treating knee cartilage lesions has several limits, including the absence of healthy articular cartilage tissues for cell isolation and difficulties related to the chondrocyte expansion in vitro. Today, various ACI modifications are being developed using autologous chondrocytes from alternative sources, such as the auricles, nose and ribs. Adult stem cells from different tissues are also of great interest due to their less traumatic material extraction and their innate abilities of active proliferation and chondrogenic differentiation. According to the different adult stem cell types and their origin, various strategies have been proposed for stem cell expansion and initiation of their chondrogenic differentiation. The current review presents the diversity in developing applied techniques based on autologous adult stem cell differentiation to hyaline cartilage tissue and targeted to articular cartilage damage therapy.
“…Several signalling pathways and transcription factors contribute to their expression and activity. One of the key pathways involved is the Wnt/β-catenin signalling pathway [47] . During the early stages of chondrogenesis, Wnt signalling is suppressed, allowing SOX9 expression and subsequent chondrocyte differentiation [47] .…”
Section: Differentiated Atdc5 Cell-derived Cdecm Is Capable Of Induci...mentioning
The prevalence of osteoarthritis has been increasing in aging populations, which has necessitated the use of advanced biomedical treatments. These involve grafts or delivering drug molecules entrapped in scaffolds. However, such treatments often show suboptimal therapeutic effects due to poor half-life and off-target effects of drug molecules. This study aims to overcome these limitations by 3D printing gelatin-based hydrogel scaffolds containing cell-derived extracellular matrix (ECM) as the bioactive therapeutic cargo. Here, pre-osteoblastic and pre-chondrogenic murine cells were differentiated in vitro, decellularized, and incorporated into methacrylated gelatin (GelMA) solutions to form osteogenic (GelO) and chondrogenic (GelC) hydrogels, respectively. The integration of the bioactive decellularized extracellular matrix (dECM) allows GelO and GelC to induce differentiation in human adipose-derived stem cells (hADSCs) toward osteogenic and chondrogenic lineages. GelO and GelC can be covalently adhered using carbodiimide coupling reaction, forming bioactive osteochondral plug. Moreover, this osteochondral plug can also induce differentiation of hADSCs. To conclude, this ECM-based bioactive hydrogel offers a promising new drug-free and cell-free treatment strategy for bone and cartilage repair, and future osteoarthritis management.
“…Wnt/β-catenin signaling activates the transcriptional activity of the target gene by β-catenin nuclear translocation and the noncanonical Wnt signaling pathway, which includes the Wnt Ca 2+ signaling pathway, 30 Wnt PCP signaling pathway, and regulation of spindle orientation and intracellular signaling pathways in asymmetric cell division. 29 This review mostly focuses on the canonical Wnt signaling pathway because of its significant function in the human body. 16 The Wnt-β-catenin signaling pathway mainly consists of the Wnt family of secreted proteins, frizzled family transmembrane receptor protein, and LRP on the cell membrane.…”
Section: Motile Ciliamentioning
confidence: 99%
“… 10 Wnt was initially discovered in mice as integration 1 (Int1). 29 Later, a homolog gene type was identified in Drosophila melanogaster with a wingless phenotype and was named Wnt. The pathway led by the Wnt gene is called the Wnt signaling pathway, and its mainly classified into the canonical Wnt signaling pathway, also known as Wnt/β-catenin signaling pathway.…”
Section: Overview Of Wnt/β-catenin Signaling Pathwaymentioning
Kinesin family member 3A is an important motor protein that participates in various physiological and pathological processes, including normal tissue development, homeostasis maintenance, tumor infiltration, and migration. The wingless-related integration site/β-catenin signaling pathway is essential for critical molecular mechanisms such as embryonic development, organogenesis, tissue regeneration, and carcinogenesis. Recent studies have examined the molecular mechanisms of kinesin family member 3A, among which the wingless-related integration site/β-catenin signaling pathway has gained attention. The interaction between kinesin family member 3A and the wingless-related integration site/β-catenin signaling pathway is compact and complex but is fascinating and worthy of further study. The upregulation and downregulation of kinesin family member 3A influence many diseases and patient survival through the wingless-related integration site/β-catenin signaling pathway. Therefore, this review mainly focuses on describing the kinesin family member 3A and wingless-related integration site/β-catenin signaling pathways and their associated diseases.
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