[en] BACKGROUND: Bones have a remarkable capacity to heal upon fracture. Yet, in large defects or compromised conditions healing processes become impaired, resulting in delayed or non-union. Current therapeutic approaches often utilize autologous or allogeneic bone grafts for bone augmentation. However, limited availability of these tissues and lack of predictive biological response result in limitations for clinical demands. Tissue engineering using viable cell-based implants is a strategic approach to address these unmet medical needs. METHODS: Herein, the in vitro and in vivo cartilage and bone tissue formation potencies of human pluripotent stem cells were investigated. The induced pluripotent stem cells were specified towards the mesodermal lineage and differentiated towards chondrocytes, which subsequently self-assembled into cartilaginous organoids. The tissue formation capacity of these organoids was then challenged in an ectopic and orthotopic bone formation model. RESULTS: The derived chondrocytes expressed similar levels of collagen type II as primary human articular chondrocytes and produced stable cartilage when implanted ectopically in vivo. Upon targeted promotion towards hypertrophy and priming with a proinflammatory mediator, the organoids mediated successful bridging of critical size long bone defects in immunocompromised mice. CONCLUSIONS: These results highlight the promise of induced pluripotent stem cell technology for the creation of functional cartilage tissue intermediates that can be explored for novel bone healing strategies.
Disciplines :
Engineering, computing & technology: Multidisciplinary, general & others
Author, co-author :
Tam, Wai Long; Laboratory for Developmental and Stem Cell Biology (DSB), Skeletal Biology and ; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1 Herestraat
Freitas Mendes, Luís; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1 Herestraat ; Laboratory for Tissue Engineering (TE), Skeletal Biology and Engineering Research
Chen, Xike; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1 Herestraat ; Laboratory for Tissue Engineering (TE), Skeletal Biology and Engineering Research
Lesage, Raphaëlle; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1 Herestraat ; Biomechmanics Section, KU Leuven, Celestijnenlaan 300C (2419), 3000, Leuven,
Van Hoven, Inge; Laboratory for Developmental and Stem Cell Biology (DSB), Skeletal Biology and ; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1 Herestraat ; Laboratory for Tissue Engineering (TE), Skeletal Biology and Engineering Research
Leysen, Elke; Laboratory for Developmental and Stem Cell Biology (DSB), Skeletal Biology and ; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1 Herestraat ; Laboratory for Tissue Engineering (TE), Skeletal Biology and Engineering Research
Kerckhofs, Greet ; Université de Liège - ULiège > Département d'aérospatiale et mécanique > Génie biomécanique ; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1 Herestraat ; Institute of Mechanics, Materials, and Civil Engineering, UCLouvain, ; Institute of Experimental and Clinical Research, UCLouvain, Woluwé-Saint-Lambert, ; Department of Materials Engineering, KU Leuven, Leuven, Belgium.
Bosmans, Kathleen; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1 Herestraat ; Laboratory for Tissue Engineering (TE), Skeletal Biology and Engineering Research
Chai, Yoke Chin; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1 Herestraat ; Laboratory for Tissue Engineering (TE), Skeletal Biology and Engineering Research ; Department of Development and Regeneration, Stem Cell Institute, KU Leuven, O&N4,
Yamashita, Akihiro; Center for iPS Cell Research and Application (CiRA), Kyoto University,
Tsumaki, Noriyuki; Center for iPS Cell Research and Application (CiRA), Kyoto University,
Geris, Liesbet ; Université de Liège - ULiège > GIGA > GIGA In silico medecine - Biomechanics Research Unit ; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1 Herestraat ; Laboratory for Tissue Engineering (TE), Skeletal Biology and Engineering Research ; Biomechmanics Section, KU Leuven, Celestijnenlaan 300C (2419), 3000, Leuven, ; GIGA In Silico Medicine, Quartier Hôpital, Avenue de l'Hôpital 11 B34, 4000,
Roberts, Scott J; Laboratory for Developmental and Stem Cell Biology (DSB), Skeletal Biology and ; Department of Comparative Biomedical Sciences, The Royal Veterinary College,
Luyten, Frank P ; Laboratory for Developmental and Stem Cell Biology (DSB), Skeletal Biology and ; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1 Herestraat ; Laboratory for Tissue Engineering (TE), Skeletal Biology and Engineering Research
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