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.
Publication Date: 2018-02-27 PubMed ID: 29485180DOI: 10.22203/eCM.v035a10Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research examines how progenitor cells in auricular cartilage can effectively generate cartilage in a 3D gel culture. This method could potentially revolutionize regenerative medicine, particularly the generation of elastic cartilage structures, by overcoming current obstacles associated with the use of chondrocytes or mesenchymal stromal cells (MSCs).
Experiment Overview
- The study focused on exploring the potential of progenitor cells present in the auricular cartilage for tissue engineering. These cells, known as AuCPCs, have shown similarities to MSCs in terms of their proliferative capacity and cell surface biomarkers.
- The researchers compared the auricular cartilage progenitor cells (AuCPCs), bone marrow-derived MSCs and auricular chondrocytes’ ability to form cartilaginous matrix within a gelatin methacryloyl (gelMA)-based hydrogel over 56 days.
Results of the Experiment
- The creators of this study noticed that just like MSCs and chondrocytes, AuCPCs also had a strong capacity to generate a cartilaginous matrix. Interestingly, the MSCs performed best in terms of matrix production and mechanical properties under the culture conditions applied in this research.
- The AuCPCs exhibited increased mRNA expression of elastin and low expression of collagen type X. Their proteoglycan production levels and mechanical properties were comparable to those of the chondrocytes.
Meaning and Implications of the Results
- The findings indicate the tissue-specific differentiation potential of AuCPCs. They demonstrated an ability to produce a biological matrix much akin to natural cartilage. This capability makes them an appealing cell source for crafting elastic cartilage tissue-engineered constructs.
- The study also highlighted the inefficient chondrogenic differentiation and endochondral ossification of neo-tissues produced from MSCs and chondrocytes. This information spotlights the pressing need for alternative cell sources for regenerative medicine strategies, a role that AuCPCs could fill.
Conclusion and Future Direction
- This research paves the way for more in-depth studies on the potential of auricular cartilage progenitor cells in tissue engineering. Determining the limitations and optimal conditions for these cells can help improve efforts in generating clinically-relevant auricular structures.
Cite This Article
APA
Otto IA, Levato R, Webb WR, Khan IM, Breugem CC, Malda J.
(2018).
Progenitor cells in auricular cartilage demonstrate cartilage-forming capacity in 3D hydrogel culture.
Eur Cell Mater, 35, 132-150.
https://doi.org/10.22203/eCM.v035a10 Publication
Researcher Affiliations
- Department of Orthopedics, University Medical Center, P.O. Box 85500, 3508 GA, Utrecht, the Netherlands.j.malda@ umcutrecht.nl.
MeSH Terms
- Animals
- Biomarkers / metabolism
- Cell Differentiation / drug effects
- Cells, Cultured
- Chondrogenesis / drug effects
- Compressive Strength
- DNA / metabolism
- Ear Cartilage / cytology
- Elastic Modulus
- Extracellular Matrix / drug effects
- Extracellular Matrix / metabolism
- Gene Expression Regulation / drug effects
- Glycosaminoglycans / metabolism
- Horses
- Hydrogels / pharmacology
- Organ Specificity / drug effects
- RNA, Messenger / genetics
- RNA, Messenger / metabolism
- Stem Cells / cytology
- Stem Cells / drug effects
- Time Factors
- Tissue Engineering / methods
Grant Funding
- MR/L02280X/1 / Medical Research Council
Citations
This article has been cited 13 times.- Liu Y, Wu W, Seunggi C, Li Z, Huang Y, Zhou K, Wang B, Chen Z, Zhang Z. The application and progress of stem cells in auricular cartilage regeneration: a systematic review.. Front Cell Dev Biol 2023;11:1204050.
- Hammad M, Veyssiere A, Leclercq S, Patron V, Baugé C, Boumédiene K. Hypoxia Differentially Affects Chondrogenic Differentiation of Progenitor Cells from Different Origins.. Int J Stem Cells 2023 Aug 30;16(3):304-314.
- Otto IA, Bernal PN, Rikkers M, van Rijen MHP, Mensinga A, Kon M, Breugem CC, Levato R, Malda J. Human adult, pediatric and microtia auricular cartilage harbor fibronectin-adhering progenitor cells with regenerative ear reconstruction potential.. iScience 2022 Sep 16;25(9):104979.
- Wang G, An Y, Zhang X, Ding P, Bi H, Zhao Z. Chondrocyte Spheroids Laden in GelMA/HAMA Hybrid Hydrogel for Tissue-Engineered Cartilage with Enhanced Proliferation, Better Phenotype Maintenance, and Natural Morphological Structure.. Gels 2021 Dec 2;7(4).
- Wang G, Zhang X, Bu X, An Y, Bi H, Zhao Z. The Application of Cartilage Tissue Engineering with Cell-Laden Hydrogel in Plastic Surgery: A Systematic Review.. Tissue Eng Regen Med 2022 Feb;19(1):1-9.
- Jessop ZM, Hague A, Dobbs TD, Stewart KJ, Whitaker IS. Facial Cartilaginous Reconstruction-A Historical Perspective, State-of-the-Art, and Future Directions.. Front Surg 2021;8:680186.
- Radeloff K, Weiss D, Hagen R, Kleinsasser N, Radeloff A. Differentiation Behaviour of Adipose-Derived Stromal Cells (ASCs) Seeded on Polyurethane-Fibrin Scaffolds In Vitro and In Vivo.. Biomedicines 2021 Aug 9;9(8).
- Hu H, Liu W, Sun C, Wang Q, Yang W, Zhang Z, Xia Z, Shao Z, Wang B. Endogenous Repair and Regeneration of Injured Articular Cartilage: A Challenging but Promising Therapeutic Strategy.. Aging Dis 2021 Jun;12(3):886-901.
- Otto IA, Capendale PE, Garcia JP, de Ruijter M, van Doremalen RFM, Castilho M, Lawson T, Grinstaff MW, Breugem CC, Kon M, Levato R, Malda J. Biofabrication of a shape-stable auricular structure for the reconstruction of ear deformities.. Mater Today Bio 2021 Jan;9:100094.
- Lv X, Sun C, Hu B, Chen S, Wang Z, Wu Q, Fu K, Xia Z, Shao Z, Wang B. Simultaneous Recruitment of Stem Cells and Chondrocytes Induced by a Functionalized Self-Assembling Peptide Hydrogel Improves Endogenous Cartilage Regeneration.. Front Cell Dev Biol 2020;8:864.
- Niermeyer WL, Rodman C, Li MM, Chiang T. Tissue engineering applications in otolaryngology-The state of translation.. Laryngoscope Investig Otolaryngol 2020 Aug;5(4):630-648.
- Childs RD, Nakao H, Isogai N, Murthy A, Landis WJ. An analytical study of neocartilage from microtia and otoplasty surgical remnants: A possible application for BMP7 in microtia development and regeneration.. PLoS One 2020;15(6):e0234650.
- Wang HC, Lin TH, Chang NJ, Hsu HC, Yeh ML. Continuous Passive Motion Promotes and Maintains Chondrogenesis in Autologous Endothelial Progenitor Cell-Loaded Porous PLGA Scaffolds during Osteochondral Defect Repair in a Rabbit Model.. Int J Mol Sci 2019 Jan 10;20(2).
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