Dataset Information

Dimethyloxaloylglycine-stimulated human bone marrow mesenchymal stem cell-derived exosomes enhance bone regeneration through angiogenesis by targeting the AKT/mTOR pathway.

ABSTRACT:

Background

Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidate agents for treating critical-sized bone defects; they promote angiogenesis and may be an alternative to cell therapy. In this study, we evaluated whether exosomes derived from bone marrow-derived MSCs (BMSCs) preconditioned with a low dose of dimethyloxaloylglycine (DMOG), DMOG-MSC-Exos, exert superior proangiogenic activity in bone regeneration and the underlying mechanisms involved.

Methods

To investigate the effects of these exosomes, scratch wound healing, cell proliferation, and tube formation assays were performed in human umbilical vein endothelial cells (HUVECs). To test the effects in vivo, a critical-sized calvarial defect rat model was established. Eight weeks after the procedure, histological/histomorphometrical analysis was performed to measure bone regeneration, and micro-computerized tomography was used to measure bone regeneration and neovascularization.

Results

DMOG-MSC-Exos activated the AKT/mTOR pathway to stimulate angiogenesis in HUVECs. This contributed to bone regeneration and angiogenesis in the critical-sized calvarial defect rat model in vivo.

Conclusions

Low doses of DMOG trigger exosomes to exert enhanced proangiogenic activity in cell-free therapeutic applications.

SUBMITTER: Liang B

PROVIDER: S-EPMC6869275 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dimethyloxaloylglycine-stimulated human bone marrow mesenchymal stem cell-derived exosomes enhance bone regeneration through angiogenesis by targeting the AKT/mTOR pathway.

Liang Bo B Liang Jia-Ming JM Ding Jia-Ning JN Xu Jia J Xu Jian-Guang JG Chai Yi-Min YM

Stem cell research & therapy 20191120 1

<h4>Background</h4>Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidate agents for treating critical-sized bone defects; they promote angiogenesis and may be an alternative to cell therapy. In this study, we evaluated whether exosomes derived from bone marrow-derived MSCs (BMSCs) preconditioned with a low dose of dimethyloxaloylglycine (DMOG), DMOG-MSC-Exos, exert superior proangiogenic activity in bone regeneration and the underlying mechanisms involved.<h4>Methods ...[more]

PMID: 31747933

Similar Datasets

Project description:Although many therapeutic interventions have shown promise in treating spinal cord injury, focusing on a single aspect of repair cannot achieve successful and functional regeneration in patients following spinal cord injury . In this study, we applied a combinatorial approach for treating spinal cord injury involving neuroprotection and rehabilitation, exploiting cell transplantation and functional sensorimotor training to promote nerve regeneration and functional recovery. Here, we used a mouse model of thoracic contusive spinal cord injury to investigate whether the combination of bone marrow mesenchymal stem cell transplantation and exercise training has a synergistic effect on functional restoration. Locomotor function was evaluated by the Basso Mouse Scale, horizontal ladder test, and footprint analysis. Magnetic resonance imaging, histological examination, transmission electron microscopy observation, immunofluorescence staining, and western blotting were performed 8 weeks after spinal cord injury to further explore the potential mechanism behind the synergistic repair effect. In vivo, the combination of bone marrow mesenchymal stem cell transplantation and exercise showed a better therapeutic effect on motor function than the single treatments. Further investigations revealed that the combination of bone marrow mesenchymal stem cell transplantation and exercise markedly reduced fibrotic scar tissue, protected neurons, and promoted axon and myelin protection. Additionally, the synergistic effects of bone marrow mesenchymal stem cell transplantation and exercise on spinal cord injury recovery occurred via the PI3K/AKT/mTOR pathway. In vitro, experimental evidence from the PC12 cell line and primary cortical neuron culture also demonstrated that blocking of the PI3K/AKT/mTOR pathway would aggravate neuronal damage. Thus, bone marrow mesenchymal stem cell transplantation combined with exercise training can effectively restore motor function after spinal cord injury by activating the PI3K/AKT/mTOR pathway.

Dataset Information

Dimethyloxaloylglycine-stimulated human bone marrow mesenchymal stem cell-derived exosomes enhance bone regeneration through angiogenesis by targeting the AKT/mTOR pathway.

Background

Methods

Results

Conclusions

Publications

Dimethyloxaloylglycine-stimulated human bone marrow mesenchymal stem cell-derived exosomes enhance bone regeneration through angiogenesis by targeting the AKT/mTOR pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets