2023, Vol. 27 ›› Issue (10): 1501-1506

Memory effect of bone marrow mesenchymal stem cells on osteogenesis after mechanical stimulation

Chen Chunxiao1, 2, Jiang Letao3, Shen Yue1, Yan Jiakai1, Li Ke1, Shi Yu1, Lin Wenzheng1, Li Hanwen4, Chen Hao1, 2, 5   

Abstract: BACKGROUND: Bone marrow mesenchymal stem cells are ideal seed cells for tissue engineering, and mechanical stimulation can guide their differentiation. It has been found that stem cells have mechanical memory, that is, the change induced by mechanical stimulation may affect the long-term fate of stem cells.  
OBJECTIVE: To investigate the memory effect of bone marrow mesenchymal stem cells on mechanical stimulation and to analyze the epigenetic mechanism.
METHODS: (1) Mouse bone marrow mesenchymal stem cells were isolated, and the differentiation ability of the three-lineage was detected for further use at passage 3. (2) Mouse bone marrow mesenchymal stem cells were stimulated using extensometer in vitro to detect osteogenic differentiation before and after stretching. (3) The stemness of cells after stretching was detected by flow cytometry. (4) The stretched and unstretched cells were re-digested into ordinary 12-well plates and cultured for 14 days to detect the osteogenic differentiation of the cells. (5) Immunofluorescence staining was used to detect and screen the key histone modification changes that cause the mechanical memory of stem cells, and to preliminarily clarify the possible mechanism of epigenetic regulation.  
RESULTS AND CONCLUSION: (1) Mechanical stimulation of 5% deformation, 0.5 Hz, 6 hours per day for 7 days could induce the differentiation of mouse bone marrow mesenchymal stem cells to osteogenic direction. (2) After reseeding plate culture, the stretched cells remained dry and continued to differentiate toward osteogenesis. (3) The results showed that bone marrow mesenchymal stem cells had epigenetic memory for mechanical stimulation, and this epigenetic memory may be related to histone H3K4me3 modification, which is induced by mechanical stimulation.
Key words: cellular mechanical memory, epigenetic modification, bone marrow mesenchymal stem cell, osteogenic differentiation, H3K4me3