Human pluripotent stem cell-derived cartilaginous organoids promote scaffold-free healing of critical size long bone defects
| Autor: | Raphaëlle Lesage, Xike Chen, Greet Kerckhofs, Frank P. Luyten, Noriyuki Tsumaki, Akihiro Yamashita, Liesbet Geris, Wai Long Tam, Elke Leysen, Kathleen Bosmans, Luis Freitas Mendes, Scott J. Roberts, Yoke Chin Chai, Inge Van Hoven |
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| Přispěvatelé: | UCL - SST/IMMC/MEED - Mechatronic, Electrical Energy, and Dynamics Systems, UCL - SSS/IREC - Institut de recherche expérimentale et clinique |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Medicine (General)
Long bone Medicine (miscellaneous) Genetics and Molecular Biology (miscellaneous) Research & Experimental Medicine Bone tissue Biochemistry Bone tissue engineering Mice 0302 clinical medicine Tissue engineering Induced pluripotent stem cell 0303 health sciences Cell biology Organoids Induced pluripotent stem cells medicine.anatomical_structure Medicine Research & Experimental Molecular Medicine Stem cell Chondrogenesis Life Sciences & Biomedicine Pluripotent Stem Cells QD415-436 Bone healing Biology Biochemistry Genetics and Molecular Biology (miscellaneous) Bone and Bones 03 medical and health sciences R5-920 Chondrocytes Organoid biology Pluripotent stem cells Cell & Tissue Engineering medicine Animals Humans Bone Endochondral ossification 030304 developmental biology 030203 arthritis & rheumatology Science & Technology Tissue Engineering Cartilage Research Cell Biology Stem cell technology |
| Zdroj: | Stem Cell Research & Therapy Stem Cell Research & Therapy, Vol 12, Iss 1, Pp 1-16 (2021) Stem Cell Research & Therapy, Vol. 12, no.1 (2021) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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