A novel method to improve the osteogenesis capacity of hUCMSCs with dual-directional pre-induction under screened co-culture conditions

Q. Rong, S. Li, Y. Zhou, Y. Geng, S. Liu, W. Wu, T. Forouzanfar, G. Wu, Z. Zhang, M. Zhou

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article numbere12740
Number of pages16
JournalCell Proliferation
Volume53
Issue number2
DOIs
Publication statusPublished - 1 Feb 2020

Funding

This work was supported by the National Nature Science Foundation of China [grant number 81671029], the National Major Science and Technology Project of China [grant number 2016YFC1102900], the Guangzhou Science, Technology and Innovation Commission [grant number 201803040008, 201704030024], the International Team for Implantology [grant number 881_2012], the Bureau of Education of Guangzhou Municipality [grant number 1201610458], the Joint Fund for Applied Basic Research of Yunnan Provincial Science and Technology Department-Kunming Medical School [grant number 2017FE468-168]. This work was supported by National Nature Science Foundation of China [grant number 81671029], National Major Science and Technology Project of China [grant number 2016YFC1102900], Guangzhou Science, Technology and Innovation Commission [grant number 201803040008, 201704030024], International Team for Implantology [grant number 881_2012], Bureau of Education of Guangzhou Municipality [grant number 1201610458], Joint Fund for Applied Basic Research of Yunnan Provincial Science and Technology Department‐Kunming Medical School [grant number 2017FE468‐168].

FundersFunder number
Joint Fund for Applied Basic Research of Yunnan Provincial Science and Technology Department-Kunming Medical School
Joint Fund for Applied Basic Research of Yunnan Provincial Science and Technology Department‐Kunming Medical School2017FE468‐168
National Natural Science Foundation of China81671029
National Aerospace Science Foundation of China
Bureau of Education of Guangzhou Municipality1201610458
Guangzhou Science, Technology and Innovation Commission201803040008, 201704030024
International Team for Implantology881_2012
National Major Science and Technology Projects of China2016YFC1102900

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