Assessing Biomaterial‐Induced Stem Cell Lineage Fate by Machine Learning‐Based Artificial Intelligence

Abstract Current functional assessment of biomaterial‐induced stem cell lineage fate in vitro mainly relies on biomarker‐dependent methods with limited accuracy and efficiency. Here a “Mesenchymal stem cell Differentiation Prediction (MeD‐P)” framework for biomaterial‐induced cell lineage fate prediction is reported. MeD‐P contains a cell‐type‐specific gene expression profile as a reference by integrating public RNA‐seq data related to tri‐lineage differentiation (osteogenesis, chondrogenesis, and adipogenesis) of human mesenchymal stem cells (hMSCs) and a predictive model for classifying hMSCs differentiation lineages using the k‐nearest neighbors (kNN) strategy. It is shown that MeD‐P exhibits an overall accuracy of 90.63% on testing datasets, which is significantly higher than the model constructed based on canonical marker genes (80.21%). Moreover, evaluations of multiple biomaterials show that MeD‐P provides accurate prediction of lineage fate on different types of biomaterials as early as the first week of hMSCs culture. In summary, it is demonstrated that MeD‐P is an efficient and accurate strategy for stem cell lineage fate prediction and preliminary biomaterial functional evaluation.