Human adult, pediatric and microtia auricular cartilage harbor fibronectin-adhering progenitor cells with regenerative ear reconstruction potential
Otto, Iris A.; Bernal, Paulina Nuñez; Rikkers, Margot; Rijen, Mattie H.P. van; Mensinga, Anneloes; Kon, Moshe; Breugem, Corstiaan C.; Levato, Riccardo; Malda, Jos
(2022) iScience, volume 25, issue 9, pp. 1 - 20
(Article)
Abstract
Remaining challenges in auricular cartilage tissue engineering include acquiring sufficient amounts of regeneration-competent cells and subsequent production of high-quality neocartilage. Progenitor cells are a resident subpopulation of native cartilage, displaying a high proliferative and cartilage-forming capacity, yet their potential for regenerative medicine is vastly understudied. In this study, human auricular
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cartilage progenitor cells were newly identified in healthy cartilage and, importantly, in microtia-impaired chondral remnants. Their cartilage repair potential was assessed via in vitro 3D culture upon encapsulation in a gelatin-based hydrogel, and subsequent biochemical, mechanical, and histological analyses. Auricular cartilage progenitor cells demonstrate a potent ability to proliferate without losing their multipotent differentiation ability and to produce cartilage-like matrix in 3D culture. As these cells can be easily obtained through a non-deforming biopsy of the healthy ear or from the otherwise redundant microtia remnant, they can provide an important solution for long-existing challenges in auricular cartilage tissue engineering.
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Keywords: Bioengineering, Health sciences, Tissue engineering, General
ISSN: 2589-0042
Publisher: Elsevier
Note: Funding Information: All tissues were obtained from biopsies of redundant tissue excised during surgery or from deceased donors who had donated their body to science, according to the guidelines of the Ethical Committee of the University Medical Center Utrecht. The authors would like to thank prof. R.L.A.W. Bleys and S. Plomp of the Department of Anatomy and Dr. L.N.A. van Adrichem of the Department of Plastic, Reconstructive and Hand Surgery of the University Medical Center Utrecht for kindly providing tissues from deceased donors and otoplasty remnants, respectively. The authors also gratefully acknowledge Iris Pennings for developing the protocol for the staining of elastin, and thank Nasim Golafshan for help with the graphical abstract. The antibody against collagen type II, developed by T.F. Linsenmayer, was obtained from the Developmental Studies Hybridoma Bank, created by the NICHD and maintained at The University of Iowa, Department of Biology, Iowa City, IA 52242, USA. The research was supported by the Netherlands Organization for Scientific Research (Graduate Program Grant 022.005.018), the Dutch Arthritis Foundation (CO-14-001, LLP-12 and LLP-22), and the European Research Council under grant agreement No. 647426 (3D-JOINT). Conceptualization by I.A.O. M.K. C.C.B. R.L. and J.M.; Methodology by I.A.O. and R.L.; Investigation by I.A.O. P.N.B. M.R. M.H.P.R. and A.M.; Formal Analysis by I.A.O. P.N.B. and M.R.; Writing of the original draft by I.A.O.; Review & Editing by I.A.O. P.N.B. R.L. and J.M.; Resources & Visualization by I.A.O. and P.N.B.; Project Administration by I.A.O.; Supervision by M.K. C.C.B. R.L. and J.M. The authors declare no competing interests. Funding Information: All tissues were obtained from biopsies of redundant tissue excised during surgery or from deceased donors who had donated their body to science, according to the guidelines of the Ethical Committee of the University Medical Center Utrecht. The authors would like to thank prof. R.L.A.W. Bleys and S. Plomp of the Department of Anatomy and Dr. L.N.A. van Adrichem of the Department of Plastic, Reconstructive and Hand Surgery of the University Medical Center Utrecht for kindly providing tissues from deceased donors and otoplasty remnants, respectively. The authors also gratefully acknowledge Iris Pennings for developing the protocol for the staining of elastin, and thank Nasim Golafshan for help with the graphical abstract. The antibody against collagen type II, developed by T.F. Linsenmayer, was obtained from the Developmental Studies Hybridoma Bank, created by the NICHD and maintained at The University of Iowa, Department of Biology, Iowa City, IA 52242, USA. The research was supported by the Netherlands Organization for Scientific Research (Graduate Program Grant 022.005.018 ), the Dutch Arthritis Foundation ( CO-14-001 , LLP-12 and LLP-22 ), and the European Research Council under grant agreement No. 647426 (3D-JOINT). Publisher Copyright: © 2022
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