scholarly journals Exosomes Derived from Bone Mesenchymal Stem Cells with the Stimulation of Fe3O4 Nanoparticles and Static Magnetic Field Enhance Wound Healing Through Upregulated miR-21-5p

2020 ◽  
Vol Volume 15 ◽  
pp. 7979-7993
Author(s):  
Di Wu ◽  
Lin Kang ◽  
Jingjing Tian ◽  
Yuanhao Wu ◽  
Jieying Liu ◽  
...  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Di Wu ◽  
Xiao Chang ◽  
Jingjing Tian ◽  
Lin Kang ◽  
Yuanhao Wu ◽  
...  

Abstract Background The therapeutic potential of exosomes derived from stem cells has attracted increasing interest recently, because they can exert similar paracrine functions of stem cells and overcome the limitations of stem cells transplantation. Exosomes derived from bone mesenchymal stem cells (BMSC-Exos) have been confirmed to promote osteogenesis and angiogenesis. The magnetic nanoparticles (eg. Fe3O4, γ-Fe2O3) combined with a static magnetic field (SMF) has been commonly used to increase wound healing and bone regeneration. Hence, this study aims to evaluate whether exosomes derived from BMSCs preconditioned with a low dose of Fe3O4 nanoparticles with or without the SMF, exert superior pro-osteogenic and pro-angiogenic activities in bone regeneration and the underlying mechanisms involved. Methods Two novel types of exosomes derived from preconditioned BMSCs that fabricated by regulating the contents with the stimulation of magnetic nanoparticles and/or a SMF. Then, the new exosomes were isolated by ultracentrifugation and characterized. Afterwards, we conducted in vitro experiments in which we measured osteogenic differentiation, cell proliferation, cell migration, and tube formation, then established an in vivo critical-sized calvarial defect rat model. The miRNA expression profiles were compared among the exosomes to detect the potential mechanism of improving osteogenesis and angiogenesis. At last, the function of exosomal miRNA during bone regeneration was confirmed by utilizing a series of gain- and loss-of-function experiments in vitro. Results 50 µg/mL Fe3O4 nanoparticles and a 100 mT SMF were chosen as the optimum magnetic conditions to fabricate two new exosomes, named BMSC-Fe3O4-Exos and BMSC-Fe3O4-SMF-Exos. They were both confirmed to enhance osteogenesis and angiogenesis in vitro and in vivo compared with BMSC-Exos, and BMSC-Fe3O4-SMF-Exos had the most marked effect. The promotion effect was found to be related to the highly riched miR-1260a in BMSC-Fe3O4-SMF-Exos. Furthermore, miR-1260a was verified to enhance osteogenesis and angiogenesis through inhibition of HDAC7 and COL4A2, respectively. Conclusion These results suggest that low doses of Fe3O4 nanoparticles combined with a SMF trigger exosomes to exert enhanced osteogenesis and angiogenesis and that targeting of HDAC7 and COL4A2 by exosomal miR-1260a plays a crucial role in this process. This work could provide a new protocol to promote bone regeneration for tissue engineering in the future. Graphical abstract


2020 ◽  
Author(s):  
Yanan Kong ◽  
Liuhanghang Cheng ◽  
Min Xuan ◽  
Hao Ding ◽  
Biao Cheng

Abstract Background Hematopoietic stem cells(HSCs) and mesenchymal stem cells(MSCs) can participate in wound healing. However, very few studies had shown HSCs and MSCs could arrive to the wound and differentiate into tissues. In this study, we intend to investigate the role of bone marrow HSCs and MSCs in wound healing. Methods We first removed the bone marrow of mice by irradiation. Furthermore, we injected different colours of fluorescent HSCs and MSCs into the tail vein of irradiated mice to reconstruct bone marrow function. We prepared wound models on the back of these mice. In vivo imaging and immunohistochemical staining were used to track the expression of fluorescent protein. Results HSCs and MSCs have been isolated and cultured. HSCs expressed expressed Sca1, not lineage, CD34 or CD48. MSCs expressed expressed CD29 and CD44,not CD34 or CD45. HSCs labeled with green fluorescent protein reached the wound and co-expressed with desmin and α-SMA. MSCs didn’t stay on the wound. Conclusions The results show HSCs in the bone marrow of mice can directly participate in wound healing and differentiate into pericytes and myofibroblasts.


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