Chinese Journal of Tissue Engineering Research ›› 2024, Vol. 28 ›› Issue (19): 3076-3083.doi: 10.12307/2024.185

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Notch signaling pathway regulates proliferation and differentiation of mesenchymal stem cells

Wang Xuesong1, 2, Zhou Lin1, 3, 4, 5, Li Lincai1, 3, 4, 5, Zou Zhengwei1, 3, 4, 5, Tang Xingkun1, 2, Lu Wenming1, 2, Chen Wenjie2, Wang Yue6, Ye Junsong1, 3, 4, 5   

  1. 1 Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China; 2 School of Rehabilitation Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China; 3 Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Ganzhou 341000, Jiangxi Province, China; 4 Key Laboratory of Medical Tissue Engineering Materials and Biological Manufacturing of Jiangxi Province,Gannan Medical University, Ganzhou 341000, Jiangxi Province, China; 5 Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China; 6 College of Nursing, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
  • Received:2023-06-17 Accepted:2023-07-29 Online:2024-07-08 Published:2023-09-26
  • Contact: Ye Junsong, PhD, Associate Professor, Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China; Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Ganzhou 341000, Jiangxi Province, China; Key Laboratory of Medical Tissue Engineering Materials and Biological Manufacturing of Jiangxi Province, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China; Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
  • About author:Wang Xuesong, Master candidate, Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China; School of Rehabilitation Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 32060232 (to YJS); Natural Science Foundation of Jiangxi Province, No. 20212BAB206057 (to YJS); Science and Technology Project of Jiangxi Provincial Health Commission, No. 20191079 (to YJS)

Abstract: BACKGROUND: It was found that the ligands and receptors of Notch are both cell membrane surface proteins, which are important proteins to mediate intercellular communication, and the Notch signaling pathway plays a crucial regulatory role in the proliferation and differentiation of mesenchymal stem cells.
OBJECTIVE: To review the regulatory mechanism of the Notch signaling pathway on the proliferation and differentiation of mesenchymal stem cells, summarize and clarify the research advance in how the Notch signaling pathway regulates the proliferation and differentiation of mesenchymal stem cells, and provide theoretical support for the future use of stem cells to treat various related diseases. 
METHODS: By using the computer, the first author searched the relevant studies involving Notch signaling pathway regulation of mesenchymal stem cell proliferation and differentiation on CNKI, Wanfang, VIP, PubMed, Web of Science, and Nature databases with Chinese search terms “mesenchymal stem cells, Notch, Notch signaling pathway, proliferation, differentiation” and the English search terms “mesenchymal stem cells, MSC, Notch, Notch signaling pathway, proliferation, differentiation”. Part of the literature was searched in combination with the literature tracing method. Finally, 87 articles were included in the review analysis. 
RESULTS AND CONCLUSION: (1) Notch signaling pathway is a conserved signaling pathway in multicellular organisms, which plays an important role in regulating cell differentiation, proliferation, apoptosis, and the cell cycle by mediating communication between neighboring cells through receptor-ligand binding. (2) Mesenchymal stem cells are a class of adult stem cells with self-proliferative and multi-directional differentiation potential, which can be regulated by external signaling pathways to affect their proliferation and differentiation. Notch signaling pathway, as one of them, when Notch ligands are activated, the Notch proteins will undergo two protein hydrolysis cleavages to release Notch intracellular structural domain NICD, which then enters the nucleus and thus promotes the transcription of target genes to regulate the proliferation and differentiation of mesenchymal stem cells from different sources, such as bone marrow, adipose, and umbilical cord. However, the specific mechanisms that regulate the proliferation and differentiation of mesenchymal stem cells from different tissue sources of the same species are different. (3) The Notch signaling pathway can regulate the differentiation of mesenchymal stem cells into different target cells, but due to different target cells, the expression levels of receptors or ligands in the Notch signaling pathway vary. (4) Clinical targeting of the Notch signaling pathway to promote mesenchymal stem cells for the treatment of various refractory diseases, such as aplastic anemia, severe joint injuries, ischemic strokes, and myocardial infarctions, has a promising application. (5) By exploring the Notch signaling pathway via regulating the expression levels of its receptors and ligands in bone marrow mesenchymal stem cells from rat, mouse, and human, it can be found that the Notch signaling pathway expression levels in the proliferation and differentiation of mesenchymal stem cells from different species origins are also different. (6) The role of mesenchymal stem cells in tissue engineering has been gradually highlighted due to their advantages of safety, low immune rejection, and wide therapeutic prospects. The Notch signaling pathway regulates the proliferation and differentiation of mesenchymal stem cells with a wide range of influencing factors, and subsequent studies should further optimize the influencing factor variables and explore the standardized studies of regulating the proliferation and differentiation of mesenchymal stem cells. 

Key words: Notch signaling pathway, signaling pathway, stem cell, mesenchymal stem cell, clinical significance, cell fate, proliferation, differentiation, review

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