Laboratory for Developmental and Stem Cell Biology (DSB), Skeletal Biology and Engineering Research Center (SBE), KU Leuven, O&N1, Herestraat 49, Onderwijs en Navorsing 8th floor, bus 813, 3000, Leuven, Belgium.
Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1 Herestraat 49 Bus 813, 3000, Leuven, Belgium.
Stem Cell Res Ther. 2021 Sep 25;12(1):513. doi: 10.1186/s13287-021-02580-7.
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.
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.
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.
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.
骨骼在骨折后具有很强的愈合能力。然而，在大的缺损或受损的情况下，愈合过程会受到损害，导致愈合延迟或不愈合。目前的治疗方法通常使用自体或同种异体骨移植物进行骨增强。然而，这些组织的有限可用性和缺乏预测性的生物反应导致了临床需求的限制。利用有活力的基于细胞的植入物进行组织工程是解决这些未满足的医疗需求的一种策略方法。
本文研究了人多能干细胞在体外和体内软骨和骨组织形成的潜力。诱导多能干细胞被指定为中胚层谱系，并分化为软骨细胞，随后这些软骨细胞自行组装成软骨类器官。然后，在异位和原位成骨模型中挑战这些类器官的组织形成能力。
衍生的软骨细胞表达与原代人关节软骨相似水平的 II 型胶原，并在体内异位植入时产生稳定的软骨。当被靶向促进肥大并被促炎介质预刺激时，这些类器官介导了免疫缺陷小鼠中临界大小长骨缺损的成功桥接。
这些结果突出了诱导多能干细胞技术在创造可用于新型骨愈合策略的功能性软骨组织中间体方面的潜力。
