Recapitulation of cartilage/bone formation using iPSCs via biomimetic 3D rotary culture approach for developmental engineering

Maolin Zhang; Junfeng Shi; Ming Xie; Jin Wen; Kunimichi Niibe; Xiangkai Zhang; Jiaxin Luo; Ran Yan; Zhiyuan Zhang; Hiroshi Egusa; Xinquan Jiang

doi:10.1016/j.biomaterials.2020.120334

Recapitulation of cartilage/bone formation using iPSCs via biomimetic 3D rotary culture approach for developmental engineering

Biomaterials. 2020 Nov:260:120334. doi: 10.1016/j.biomaterials.2020.120334. Epub 2020 Aug 17.

Authors

Maolin Zhang¹, Junfeng Shi², Ming Xie², Jin Wen², Kunimichi Niibe³, Xiangkai Zhang⁴, Jiaxin Luo², Ran Yan², Zhiyuan Zhang⁴, Hiroshi Egusa⁵, Xinquan Jiang⁶

Affiliations

¹ Department 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.
² Department 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.
³ Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-Ku, Sendai, Miyagi, 980-8575, Japan.
⁴ Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Road, Shanghai, 200011, China.
⁵ Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-Ku, Sendai, Miyagi, 980-8575, Japan. Electronic address: egu@dent.tohoku.ac.jp.
⁶ Department 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. Electronic address: xinquanj@aliyun.com.

PMID: 32862124
DOI: 10.1016/j.biomaterials.2020.120334

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.

Keywords: 3D rotary culture; Bone regeneration; Cartilage regeneration; Endochondral ossification; Mechanical stimuli; iPSCs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomimetics
Cartilage
Cell Differentiation
Chondrocytes
Chondrogenesis
Induced Pluripotent Stem Cells*
Osteogenesis*