IADR Abstract Archives
In vivo Therapeutic Efficacy of MSC Exosomes for Bone Regeneration
Objectives:
Treating critical-sized bone defects in craniofacial region is a major challenge in the healthcare sector. Current bone grafting techniques have significant limitations including lack of availability, donor site morbidity and reduced healing potential. Exosomes, extracellular vesicles functioning as cell-to-cell communicators, have been proposed as a promising bone regenerative agent. Previously using osteoblasts and endothelial cell cultures, we demonstrated human mesenchymal stem cell (MSC) exosomes possesses potent ability to enhance osteogenesis and angiogenesis in vitro. The aim of this preliminary study was to evaluate the in vivo efficacy of human MSC exosomes in bone regeneration using a rat calvarial defect model.
Methods: Exosomes were purified from conditioned medium of human MSCs. Thirty-two rats, each with surgically created one critical-sized calvarial bone defect (8mm diameter), were randomly assigned into four groups (n=8). Three experimental groups received 50, 100, and 200 µg/ml of MSC exosomes loaded in fibrin gel while the control group received only fibrin gel. Animals were sacrificed at 4 and 8 weeks post-operatively and new bone formation was evaluated by micro-CT, histology, histomorphometry and immunohistochemistry analyses.
Results:
Micro-CT analysis showed dose-dependent increase in new bone formation in exosome treated groups at 4 weeks. Concentration of 200 µg/ml exosomes had significantly higher percentage of new bone volume (BV/TV) compared to the control and other groups (P<0.05). Histological observations based on H&E and Masson’s staining revealed that exosome treatment significantly increased the newly formed bone tissues within the defect areas (P<0.05). Immunohistochemical staining of the newly formed bone area in the exosome treated groups showed positive expressions of key osteogenic markers OCN, ALP and BMP2.
Conclusions:
The foregoing results indicate the promising potential of MSC exosomes in bone repair and regeneration. Future clinical trials should aim to establish further evidence on MSC exosomes as a therapeutic modality for craniofacial bony defects.
Treating critical-sized bone defects in craniofacial region is a major challenge in the healthcare sector. Current bone grafting techniques have significant limitations including lack of availability, donor site morbidity and reduced healing potential. Exosomes, extracellular vesicles functioning as cell-to-cell communicators, have been proposed as a promising bone regenerative agent. Previously using osteoblasts and endothelial cell cultures, we demonstrated human mesenchymal stem cell (MSC) exosomes possesses potent ability to enhance osteogenesis and angiogenesis in vitro. The aim of this preliminary study was to evaluate the in vivo efficacy of human MSC exosomes in bone regeneration using a rat calvarial defect model.
Methods: Exosomes were purified from conditioned medium of human MSCs. Thirty-two rats, each with surgically created one critical-sized calvarial bone defect (8mm diameter), were randomly assigned into four groups (n=8). Three experimental groups received 50, 100, and 200 µg/ml of MSC exosomes loaded in fibrin gel while the control group received only fibrin gel. Animals were sacrificed at 4 and 8 weeks post-operatively and new bone formation was evaluated by micro-CT, histology, histomorphometry and immunohistochemistry analyses.
Results:
Micro-CT analysis showed dose-dependent increase in new bone formation in exosome treated groups at 4 weeks. Concentration of 200 µg/ml exosomes had significantly higher percentage of new bone volume (BV/TV) compared to the control and other groups (P<0.05). Histological observations based on H&E and Masson’s staining revealed that exosome treatment significantly increased the newly formed bone tissues within the defect areas (P<0.05). Immunohistochemical staining of the newly formed bone area in the exosome treated groups showed positive expressions of key osteogenic markers OCN, ALP and BMP2.
Conclusions:
The foregoing results indicate the promising potential of MSC exosomes in bone repair and regeneration. Future clinical trials should aim to establish further evidence on MSC exosomes as a therapeutic modality for craniofacial bony defects.