Human adult, pediatric and microtia auricular cartilage harbor fibronectin-adhering progenitor cells with regenerative ear reconstruction potential
Iris A. Otto,
Paulina Nuñez Bernal,
Margot Rikkers,
Mattie H.P. van Rijen,
Anneloes Mensinga,
Moshe Kon,
Corstiaan C. Breugem,
Riccardo Levato,
Jos Malda
Affiliations
Iris A. Otto
Department of Orthopaedics, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, the Netherlands; Department of Plastic, Reconstructive and Hand Surgery, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, the Netherlands
Paulina Nuñez Bernal
Department of Orthopaedics, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, the Netherlands
Margot Rikkers
Department of Orthopaedics, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, the Netherlands
Mattie H.P. van Rijen
Department of Orthopaedics, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, the Netherlands
Anneloes Mensinga
Department of Orthopaedics, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, the Netherlands
Moshe Kon
Department of Plastic, Reconstructive and Hand Surgery, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, the Netherlands
Corstiaan C. Breugem
Department of Plastic, Reconstructive and Hand Surgery, Amsterdam University Medical Center, Emma Children’s Hospital, Meibergdreef 9, Amsterdam, 1105 ZA, the Netherlands
Riccardo Levato
Department of Orthopaedics, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, the Netherlands; Department of Clinical Sciences, Faculty of Veterinary Science, Utrecht University, Yalelaan 108, Utrecht, 3584 CM, the Netherlands; Corresponding author
Jos Malda
Department of Orthopaedics, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, the Netherlands; Department of Clinical Sciences, Faculty of Veterinary Science, Utrecht University, Yalelaan 108, Utrecht, 3584 CM, the Netherlands; Corresponding author
Summary: 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 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.