Early Predicting Osteogenic Differentiation of Mesenchymal Stem Cells Based on Deep Learning Within One Day.

Journal: Annals of biomedical engineering
PMID:

Abstract

Osteogenic differentiation of mesenchymal stem cells (MSCs) is proposed to be critical for bone tissue engineering and regenerative medicine. However, the current approach for evaluating osteogenic differentiation mainly involves immunohistochemical staining of specific markers which often can be detected at day 5-7 of osteogenic inducing. Deep learning (DL) is a significant technology for realizing artificial intelligence (AI). Computer vision, a branch of AI, has been proved to achieve high-precision image recognition using convolutional neural networks (CNNs). Our goal was to train CNNs to quantitatively measure the osteogenic differentiation of MSCs. To this end, bright-field images of MSCs during early osteogenic differentiation (day 0, 1, 3, 5, and 7) were captured using a simple optical phase contrast microscope to train CNNs. The results showed that the CNNs could be trained to recognize undifferentiated cells and differentiating cells with an accuracy of 0.961 on the independent test set. In addition, we found that CNNs successfully distinguished differentiated cells at a very early stage (only 1 day). Further analysis showed that overall morphological features of MSCs were the main basis for the CNN classification. In conclusion, MSCs differentiation detection can be achieved early and accurately through simple bright-field images and DL networks, which may also provide a potential and novel method for the field of cell detection in the near future.

Authors

  • Qiusheng Shi
    Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, No. 37 Xueyuan Road, Haidian District, Beijing, 100191, China.
  • Fan Song
    Bioinformatics and Genomics Program, The Pennsylvania State University, University Park, State College, PA, 16802, USA.
  • Xiaocheng Zhou
    Department of Statistics, The Chinese University of Hong Kong, Sha Tin, Hong Kong SAR, China.
  • Xinyuan Chen
    National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
  • Jingqi Cao
    Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, No. 37 Xueyuan Road, Haidian District, Beijing, 100191, China.
  • Jing Na
  • Yubo Fan
    State Key Laboratory of Software Development Environment, Key Laboratory of Biomechanics and Mechanobiology of Ministry of Education, Beihang University, Beijing, China. yubofan@buaa.edu.cn.
  • Guanglei Zhang
    Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing, 100191, China; School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, China. Electronic address: guangleizhang@buaa.edu.cn.
  • Lisha Zheng
    Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, No. 37 Xueyuan Road, Haidian District, Beijing, 100191, China. lishazheng@buaa.edu.cn.