Progenitor cells in auricular cartilage demonstrate cartilage-forming capacity in 3D hydrogel culture

Abstract

Paramount for the generation of auricular structures of clinically-relevant size is the acquisition of a large number of cells maintaining an elastic cartilage phenotype, which is the key in producing a tissue capable of withstanding forces subjected to the auricle. Current regenerative medicine strategies utilize chondrocytes from various locations or mesenchymal stromal cells (MSCs). However, the quality of neo-tissues resulting from these cell types is inadequate due to inefficient chondrogenic differentiation and endochondral ossification, respectively. Recently, a subpopulation of stem/progenitor cells has been identified within the auricular cartilage tissue, with similarities to MSCs in terms of proliferative capacity and cell surface biomarkers, but their potential for tissue engineering has not yet been explored. This study compared the in vitro cartilage-forming ability of equine auricular cartilage progenitor cells (AuCPCs), bone marrow-derived MSCs and auricular chondrocytes in gelatin methacryloyl (gelMA)-based hydrogels over a period of 56 d, by assessing their ability to undergo chondrogenic differentiation. Neocartilage formation was assessed through gene expression profiling, compression testing, biochemical composition and histology. Similar to MSCs and chondrocytes, AuCPCs displayed a marked ability to generate cartilaginous matrix, although, under the applied culture conditions, MSCs outperformed both cartilage-derived cell types in terms of matrix production and mechanical properties. AuCPCs demonstrated upregulated mRNA expression of elastin, low expression of collagen type X and similar levels of proteoglycan production and mechanical properties as compared to chondrocytes. These results underscored the AuCPCs' tissue-specific differentiation potential, making them an interesting cell source for the next generation of elastic cartilage tissue-engineered constructs.

Tissue engineering applications in otolaryngology—The state of translation

“…Heatmap representing the proportion of publications by year that utilized specific translational research methodologies from construct characterization to human trial to investigate otologic tissue engineering 15,25‐35,38‐43,45,46,107‐144 …”

An analytical study of neocartilage from microtia and otoplasty surgical remnants: A possible application for BMP7 in microtia development and regeneration

“…In addition, many tissues appear to support resident stem cells that are quiescent in the microenvironment of their ECM and are activated upon injury for the purpose of repair [50,51]. Indeed, different subsets of tissue-resident stem cells or cartilage stem/progenitor cells have been identified in both auricular perichondrium and auricular cartilage [52][53][54]. BMP7 has been shown to be active in mediating mesenchymal stem cell recruitment and pathways of chondrogenic maturation and is expressed specifically during the differentiation of stems cells to progenitor cells to chondroblasts [55].…”

“…Finally, DDX17 mediates cell division and growth through translation initiation and processes involving alteration of RNA secondary structure (https://www.ncbi.nlm.nih.gov/gene/10521). These differentially upregulated genes in the microtia cells with BMP7 compared to normal cells with BMP7 function as promoters of cell proliferation and growth, and their presence may indicate that different pathways or different cellular subtypes as described above are activated in microtia neocartilage formation compared to pathways activated for normal cells supplemented with BMP7 [52][53][54].…”

Human chondrocyte-conditioned medium promotes chondrogenesis of bone marrow stem cells

“…The assay was followed by a melt curve analysis to ensure PCR product specificity. Table 1 shows the primer sequence used for RT-PCR following previous studies [42][43][44]. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as the reference gene.…”