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Updated: Dec 10, 2025
Generating Spheroids from Various Chondrocytes using Low-Adhesive Conditions under Gravity and Homemade Mini-Bioreactors
Published on: January 31, 2025
Recapitulation of cartilage/bone formation using iPSCs via biomimetic 3D rotary culture approach for developmental
Maolin Zhang1, Junfeng Shi2, Ming Xie2
1Department of Prosthodontics, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China; Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-Ku, Sendai, Miyagi, 980-8575, Japan.
Abstract:
The recapitulation of cartilage/bone formation via guiding induced pluripotent stem cells (iPSCs) differentiation toward chondrogenic mesoderm lineage is an ideal approach to investigate cartilage/bone development and also for cartilage/bone regeneration. However, current induction protocols are time-consuming and complicated to follow. Here, we established a rapid and efficient approach that directly induce iPSCs differentiation toward chondrogenic mesoderm lineage by regulating the crucial Bmp-4 and FGF-2 signaling pathways using a 3D rotary suspension culture system. The mechanical stimulation from 3D rotary suspension accelerates iPSCs differentiation toward mesodermal and subsequent chondrogenic lineage via the Bmp-4-Smad1 and Tgf-β-Smad2/3 signaling pathways, respectively. The scaffold-free homogenous cartilaginous pellets or hypertrophic cartilaginous pellets derived from iPSCs within 28 days were capable of articular cartilage regeneration or vascularized bone regeneration via endochondral ossification in vivo, respectively. This biomimetic culture approach will contribute to research related to cartilage/bone development, regeneration, and hence to therapeutic applications in cartilage-/bone-related diseases.
