Angiogenesis and bone regeneration by mesenchymal stem cell transplantation with danshen in a rabbit model of avascular necrotic femoral head

Abstract

The present study aimed to explore the potential of combined treatment with mesenchymal stem cells (MSCs) and danshen for angiogenesis and bone regeneration in a rabbit model of avascular necrosis of femoral head (ANFH). A rabbit model of ANFH was established using the Shwartzman reaction with methylprednisolone and Escherichia coli endotoxin injection. Magnetic resonance imaging (MRI) and histopathological examination were used to evaluate the rabbit model of ANFH. The rabbits were randomly divided into the danshen group, the MSCs group, the danshen combined with MSCs group and the model group (treated with physiological saline). The expression level of monocyte chemoattractant protein-1 (MCP-1) and stromal cell-derived factor-1 (SDF-1) were determined by reverse transcription polymerase chain reaction (RT-PCR). The expression level of bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) were detected by immunofluorescence and the mRNA expression of BMP-2 and VEGF were detected by RT-PCR. Typical osteonecrosis occurred in the rabbit model of ANFH, which indicated that the model was successfully established. MCP-1 and SDF-1 were significantly increased in the model group compared with the normal group (P<0.05). Following the administration of MSCs and Salvia miltiorrhiza (danshen), MSCs labeled with 5-bromo-2-deoxyuridine were observed to be gathered in the necrotic area. The increased migration of MSCs to the necrotic area may be due to the upregulated expression of the chemokines MCP-1 and SDF-1. ANFH treated with danshen combined with MSCs may promote revascularization by increasing the expression of VEGF and BMP-2 in the femoral head, promoting re-ossification and revascularization. Danshen combined with the transplantation of MSCs may be regarded as a novel therapy for the treatment of ANFH in a clinical setting.

Cryogenic 3D Printing of ß-TCP/PLGA Composite Scaffolds Incorporated With BpV (Pic) for Treating Early Avascular Necrosis of Femoral Head

“…To date, ANFH is still a great challenge to orthopedic surgeons as the exact mechanisms remain unclear. It is characterized by bone ischemia and destruction of the microstructure, resulting in increased adipose vacuoles and collapse of the femoral head ( Pierce et al, 2019 ; Wu et al, 2019 ). BMSCs are capable to differentiate into various cell types including osteoblasts, adipocytes, myoblasts and chondrocytes ( Liu R. et al, 2019 ; Zheng et al, 2020 ).…”

<p>Exfoliated Human Deciduous Tooth Stem Cells Incorporating Carbonate Apatite Scaffold Enhance BMP-2, BMP-7 and Attenuate MMP-8 Expression During Initial Alveolar Bone Remodeling in Wistar Rats (<em>Rattus norvegicus</em>)</p>

“…18 A previous study conducted by Wu and team stated that post-transplantation of MSCs in a rabbit model of avascular necrosis of femoral head can enhance the BMP-2 expression level that stimulates in vivo revascularization and bone remodeling of the afflicted area. 34 Meanwhile, a study conducted by Liu and team mentions the significantly increased expression of BMP-7 in BMSCs in vitro culture indicating that the enhancement of BMP-7 expression can be used as BMSCbased cell therapy for osteoarthritis. 35 The results of those studies were in line with and support the findings of the authors that showed post-transplantation of SHED can stimulate the enhancement of BMP-2 and BMP-7 in the alveolar bone defect area.…”

Bone Regeneration Therapy of Atraumatic Necrosis of Femoral Head

“…The researchers found a high level of interleukin-6 and tumor necrosis factor-α at an advanced stage of FHN. Thus it was found that cytokine activity accelerated when used in combination with growth factor, which can be further used in future studies [70][71][72][73][74][75][76] .…”