scholarly journals Macrophage-Derived Exosomes Promote Bone Mesenchymal Stem Cells Towards Osteoblastic Fate Through microRNA-21a-5p

Author(s):  
Kun Liu ◽  
Xin Luo ◽  
Zhao-Yong Lv ◽  
Yu-Jue Zhang ◽  
Zhen Meng ◽  
...  

The effective healing of a bone defect is dependent on the careful coordination of inflammatory and bone-forming cells. In the current work, pro-inflammatory M1 and anti-inflammatory M2 macrophages were co-cultured with primary murine bone mesenchymal stem cells (BMSCs), in vitro, to establish the cross-talk among polarized macrophages and BMSCs, and as well as their effects on osteogenesis. Meanwhile, macrophages influence the osteogenesis of BMSCs through paracrine forms such as exosomes. We focused on whether exosomes of macrophages promote osteogenic differentiation. The results indicated that M1 and M2 polarized macrophage exosomes all can promote osteogenesis of BMSCs. Especially, M1 macrophage-derived exosomes promote osteogenesis of BMSCs through microRNA-21a-5p at the early stage of inflammation. This research helps to develop an understanding of the intricate interactions among BMSCs and macrophages, which can help to improve the process of bone healing as well as additional regenerative processes by local sustained release of exosomes.

Author(s):  
Fatemeh Hejazi ◽  
Vahid Ebrahimi ◽  
Mehrdad Asgary ◽  
Abbas Piryaei ◽  
Mohammad Javad Fridoni ◽  
...  

AbstractOsteoporosis is a common bone disease that results in elevated risk of fracture, and delayed bone healing and impaired bone regeneration are implicated by this disease. In this study, Elastin/Polycaprolactone/nHA nanofibrous scaffold in combination with mesenchymal stem cells were used to regenerate bone defects. Cytotoxicity, cytocompatibility and cellular morphology were evaluated in vitro and observations revealed that an appropriate environment for cellular attachment, growth, migration, and proliferation is provided by this scaffold. At 3 months following ovariectomy (OVX), the rats were used as animal models with an induced critical size defect in the femur to evaluate the therapeutic potential of osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) seeded on 3 dimension (3D) scaffolds. In this experimental study, 24 female Wistar rats were equally divided into three groups: Control, scaffold (non-seeded BM-MSC), and scaffold + cell (seeded BM-MSC) groups. 30 days after surgery, the right femur was removed, and underwent a stereological analysis and RNA extraction in order to examine the expression of Bmp-2 and Vegf genes. The results showed a significant increase in stereological parameters and expression of Bmp-2 and Vegf in scaffold and scaffold + cell groups compared to the control rats. The present study suggests that the use of the 3D Elastin/Polycaprolactone (PCL)/Nano hydroxyapatite (nHA) scaffold in combination with MSCs may improve the fracture regeneration and accelerates bone healing at the osteotomy site in rats.


2017 ◽  
Vol 46 ◽  
pp. 156-162 ◽  
Author(s):  
Chen Lv ◽  
Shengwu Yang ◽  
Xin Chen ◽  
Xiongbai Zhu ◽  
Wenjun Lin ◽  
...  

2016 ◽  
Vol 367 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Hua-ji Jiang ◽  
Xing-gui Tian ◽  
Shou-bin Huang ◽  
Guo-rong Chen ◽  
Min-jun Huang ◽  
...  

RSC Advances ◽  
2019 ◽  
Vol 9 (16) ◽  
pp. 9117-9125
Author(s):  
Ting Ma ◽  
Xi-Yuan Ge ◽  
Ke-Yi Hao ◽  
Xi Jiang ◽  
Yan Zheng ◽  
...  

Titanium discs with simple 3,4-dihydroxy-l-phenylalanine coating enhanced BM-MSC adhesion, spreading, proliferation and differentiation, and upregulated expression of genes involved in focal adhesion in vitro.


2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Jun Zhang ◽  
Ziming Liu ◽  
Yuwan Li ◽  
Qi You ◽  
Jibin Yang ◽  
...  

Background. FGF-2 (basic fibroblast growth factor) has a positive effect on the proliferation and differentiation of many kinds of MSCs. Therefore, it represents an ideal molecule to facilitate tendon-to-bone healing. Nonetheless, no studies have investigated the application of FGF-2-induced human amniotic mesenchymal stem cells (hAMSCs) to accelerate tendon-to-bone healing in vivo. Objective. The purpose of this study was to explore the effect of FGF-2 on chondrogenic differentiation of hAMSCs in vitro and the effect of FGF-2-induced hAMSCs combined with a human acellular amniotic membrane (HAAM) scaffold on tendon-to-bone healing in vivo. Methods. In vitro, hAMSCs were transfected with a lentivirus carrying the FGF-2 gene, and the potential for chondrogenic differentiation of hAMSCs induced by the FGF-2 gene was assessed using immunofluorescence and toluidine blue (TB) staining. HAAM scaffold was prepared, and hematoxylin and eosin (HE) staining and scanning electron microscopy (SEM) were used to observe the microstructure of the HAAM scaffold. hAMSCs transfected with and without FGF-2 were seeded on the HAAM scaffold at a density of 3×105 cells/well. Immunofluorescence staining of vimentin and phalloidin staining were used to confirm cell adherence and growth on the HAAM scaffold. In vivo, the rabbit extra-articular tendon-to-bone healing model was created using the right hind limb of 40 New Zealand White rabbits. Grafts mimicking tendon-to-bone interface (TBI) injury were created and subjected to treatment with the HAAM scaffold loaded with FGF-2-induced hAMSCs, HAAM scaffold loaded with hAMSCs only, HAAM scaffold, and no special treatment. Macroscopic observation, imageological analysis, histological assessment, and biomechanical analysis were conducted to evaluate tendon-to-bone healing after 3 months. Results. In vitro, cartilage-specific marker staining was positive for the FGF-2 overexpression group. The HAAM scaffold displayed a netted structure and mass extracellular matrix structure. hAMSCs or hAMSCs transfected with FGF-2 survived on the HAAM scaffold and grew well. In vivo, the group treated with HAAM scaffold loaded with FGF-2-induced hAMSCs had the narrowest bone tunnel after three months as compared with other groups. In addition, macroscopic and histological scores were higher for this group than for the other groups, along with the best mechanical strength. Conclusion. hAMSCs transfected with FGF-2 combined with the HAAM scaffold could accelerate tendon-to-bone healing in a rabbit extra-articular model.


2016 ◽  
Vol 8 (30) ◽  
pp. 19739-19746 ◽  
Author(s):  
Beibei Ding ◽  
Huichang Gao ◽  
Jianhui Song ◽  
Yaya Li ◽  
Lina Zhang ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Yannan Hu ◽  
Ning Li ◽  
Liang Liu ◽  
Hao Zhang ◽  
Xiang Xue ◽  
...  

Background. Tbx18 is a vital transcription factor involved in embryonic sinoatrial node (SAN) formation process but is gradually vanished after birth. Myocardial injection of lentiviral Tbx18 converts cardiomyocytes into pacemaker-like cells morphologically and functionally. In this in vitro and in vivo study, genetical modification of porcine bone mesenchymal stem cells (BMSCs) by recapturing the Tbx18 expression creates a biological pacemaker which was examined. Methods. The isolated porcine BMSCs were transfected with lentiviral Tbx18, and the induced pacemaker-like cells were analyzed using real-time polymerase chain reaction and western blotting to investigate the efficiency of transformation. Then, the induced pacemaker-like cells were implanted into the right ventricle of the SAN dysfunction porcine model after the differentiation process. Biological pacemaker activity and ectopic pacing region were tested by an electrocardiograph (ECG) monitor. Results. The isolated porcine BMSCs expressed specific surface markers of stem cells; meanwhile, the expression of myocardial markers was upregulated significantly after lentiviral Tbx18 transfection. The porcine SAN dysfunction model was constructed by electrocoagulation using a surgical electrotome. The results showed that the mean heart beat (HR) of BMSCs-Tbx18 was significantly higher than that of BMSCs-GFP. An ectopic pacing region was affirmed into the right ventricle by ECG after implantation of BMSCs-Tbx18. Conclusion. It was verified that Lenti-Tbx18 is capable of transducing porcine BMSCs into pacemaker-like cells. Genetically modified porcine BMSCs by lentiviral Tbx18 could create a biological pacemaker. However, further researches in large-scale animals are required to rule out unexpected complications prior to application in clinical practice.


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