Open AccessA novel method to improve the osteogenesis capacity of hUCMSCs with dual‐directional pre‐induction under screened co‐culture conditions
Author(s) -
Rong Qiong,
Li Shuyi,
Zhou Yang,
Geng Yuanming,
Liu Shangbin,
Wu Wanqiu,
Forouzanfar Tim,
Wu Gang,
Zhang Zhiyong,
Zhou Miao
Publication year - 2020
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12740
Subject(s) - mesenchymal stem cell , scaffold , angiogenesis , biomedical engineering , microbiology and biotechnology , chemistry , medicine , biology , cancer research
Objectives Mesenchymal stem cells (MSCs) based therapy for bone regeneration has been regarded as a promising method in the clinic. However, hBMSCs with invasive harvesting process and undesirable proliferation rate hinder the extensive usage. HUCMSCs of easier access and excellent performances provide an alternative for the fabrication of tissue‐engineered bone construct. Evidence suggested the osteogenesis ability of hUCMSCs was weaker than that of hBMSCs. To address this issue, a co‐culture strategy of osteogenically and angiogenically induced hUCMSCs has been proposed since thorough vascularization facilitates the blood‐borne nutrition and oxygen to transport in the scaffold, synergistically expediting the process of ossification. Materials and methods Herein, we used osteogenic‐ and angiogenic‐differentiated hUCMSCs for co‐culture in screened culture medium to elevate the osteogenic capacity with in vitro studies and finally coupled with 3D TCP scaffold to repair rat's critical‐sized calvarial bone defect. By dual‐directional induction, hUCMSCs could differentiate into osteoblasts and endothelial cells, respectively. To optimize the co‐culture condition, gradient ratios of dual‐directional differentiated hUCMSCs co‐cultured under different medium were studied to determine the appropriate condition. Results It revealed that the osteogenic‐ and angiogenic‐induced hUCMSCs mixed with the ratio of 3:1 co‐cultured in the mixed medium of osteogenic induction medium to endothelial cell induction medium of 3:1 possessed more mineralization nodules. Similarly, ALP and osteogenesis/angiogenesis‐related genes expressions were relatively higher. Further evidence of bone defect repair with 3D printed TCP of 3:1 group exhibited better restoration outcomes. Conclusions Our work demonstrated a favourable and convenient approach of dual‐directional differentiated hUCMSCs co‐culture to improve the osteogenesis, establishing a novel way to fabricate tissue‐engineered bone graft with 3D TCP for large bone defect augmentation.