Establishing stable and highly osteogenic hiPSC-derived MSCs for 3D-printed bone graft through microenvironment modulation by CHIR99021-treated osteocytes
作者全名：Guo, Qiuling; Chen, Jingjing; Bu, Qiqi; Zhang, Jinling; Ruan, Minjie; Chen, Xiaoyu; Zhao, Mingming; Tu, Xiaolin; Zhao, Chengzhu
作者地址：[Guo, Qiuling; Chen, Jingjing; Bu, Qiqi; Zhang, Jinling; Ruan, Minjie; Tu, Xiaolin; Zhao, Chengzhu] Chongqing Med Univ, Coll Lab Med, Lab Skeletal Dev & Regenerat, Key Lab Clin Lab Diagnost,Minist Educ, Chongqing 400016, Peoples R China; [Chen, Xiaoyu; Zhao, Mingming] Chongqing Med Univ, Ctr Med Epigenet, Sch Basic Med Sci, Chongqing 400016, Peoples R China
通信作者：Tu, XL; Zhao, CZ (通讯作者)，Chongqing Med Univ, Coll Lab Med, Lab Skeletal Dev & Regenerat, Key Lab Clin Lab Diagnost,Minist Educ, Chongqing 400016, Peoples R China.
来源：MATERIALS TODAY BIO
ESI学科分类：
WOS号：WOS:001252015600001
JCR分区：Q1
影响因子：8.7
年份：2024
卷号：26
期号：
开始页：
结束页：
文献类型：Article
关键词：Human induced pluripotent stem cell; Mesenchymal stem cell; Osteogenic microenvironment; 3D bioprinting; Wnt signalling
摘要：Human induced pluripotent stem cell (hiPSC)-derived mesenchymal stem cells (iMSCs) are ideal candidates for the production of standardised and scalable bioengineered bone grafts. However, stable induction and osteogenic differentiation of iMSCs pose challenges in the industry. We developed a precise differentiation method to produce homogeneous and fully differentiated iMSCs. In this study, we established a standardised system to prepare iMSCs with increased osteogenic potential and improved bioactivity by introducing a CHIR99021 (C91)treated osteogenic microenvironment (COOME). COOME enhances the osteogenic differentiation and mineralisation of iMSCs via canonical Wnt signalling. Global transcriptome analysis and co-culturing experiments indicated that COOME increased the pro-angiogenesis/neurogenesis activity of iMSCs. The superior osteogenic differentiation and mineralisation abilities of COOME-treated iMSCs were also confirmed in a Bio3D module generated using a polycaprolactone (PCL) and cell-integrated 3D printing (PCI3D) system, which is the closest model to in vivo research. This COOME-treated iMSCs differentiation system offers a new perspective for generating highly osteogenic, bioactive, and anatomically matched grafts for clinical applications. Statement of significance: Although human induced pluripotent stem cell-derived MSCs (iMSCs) are ideal seed cells for synthetic bone implants, the challenges of stable induction and osteogenic differentiation hinder their clinical application. This study established a standardised system for the scalable preparation of iMSCs with improved osteogenic potential by combining our precise iMSC differentiation method with the CHIR99021 (C91)-treated osteocyte osteogenic microenvironment (COOME) through the activation of canonical Wnt signalling. Moreover, COOME upregulated the pro-angiogenic and pro-neurogenic capacities of iMSCs, which are crucial for the integration of implanted bone grafts. The superior osteogenic ability of COOME-treated iMSCs was confirmed in Bio3D modules generated using PCL and cell-integrated 3D printing systems, highlighting their functional potential in vivo. This study contributes to tissue engineering by providing insights into the functional differentiation of iMSCs for bone regeneration.
基金机构：Young Scientists Fund of the National Natural Science Foundation of China [82202655]; National Natural Science Foundation of China [U1601220, 82072450]; Chongqing Natural Science Foundation Innovation and Development Joint Fund [CSTB2022NSCQ-LZX0048]; CQMU Program for Youth Innovation in Future Medicine [W0144]
基金资助正文：This work was supported by the Young Scientists Fund of the National Natural Science Foundation of China (Grant No. 82202655) to C. Z., National Natural Science Foundation of China (U1601220, 82072450) , Chongqing Natural Science Foundation Innovation and Development Joint Fund (CSTB2022NSCQ-LZX0048) to X.T., and CQMU Program for Youth Innovation in Future Medicine (W0144) to M. Z.
