Porcine brain extract promotes osteogenic differentiation of bone marrow derived mesenchymal stem cells and bone consolidation in a rat distraction osteogenesis model

Abstract

Distraction osteogenesis (DO) is the gold standard to treat large bone defects, but long consolidation period is a major limitation. Innovative efforts to promote osteogenesis are needed. Porcine brain extract (PBE) was reported to enhance the proliferation and differentiation of multiple primary cells. In this study, we aimed to develop a method for collecting PBE and investigate its effects on osteogenic differentiation of rat bone marrow derived mesenchymal stem cells (rBMSCs) and bone consolidation in a rat DO model. The PBE was collected from neonatal brain tissues of porcine fetus and was used to treat rBMSCs. Following PBE treatment (700 ng/ml), osteogenic differentiation was assessed. Further, we locally injected PBE (7 μg/ml, 100μl) or PBS (100μl) into the gap in a Sprague-Dawley (SD) male rat DO model every three days till termination. X-rays, micro-computed tomography, mechanical testing, histology and immunohischemistry examinations were used to exam the quality of the regenerates. The alkaline phosphatase, calcium deposits, and steogenic markers in the PBE treated rBMSCs were significantly increased. In the rat model, new bone properties of bone volume/total tissue volume and mechanical strength were higher in the PBE treated group. Histological analysis also confirmed more mineralized bone after PBE treatment. The current study reports a standard protocol for PBE collection and demonstrated its positive effects on osteogenic differentiation and bone consolidation in DO. Since the PBE is readily available and very cost effective, PBE may be a potential new bio-source to promote bone formation in patients undergo DO treatment.

Extracellular vesicles derived from T-cell acute lymphoblastic leukemia inhibit osteogenic differentiation of bone marrow mesenchymal stem cells <i>via</i> miR-34a-5p

“…Previous evidence suggests a link between osteogenesis and neurogenesis from an evolutionary perspective [43]. Porcine brain extract (PBE) promoted osteogenic differentiation of rBMSCs in a rat DO model, and there are multiple factors in PBE, particularly neuronal growth factors, which are important for promoting bone regeneration [44]. Therefore, we speculated that a link exists between neurogenesis and osteogenesis; however, the relationship between neurogenesis and osteogenesis and which plays a key role during bone formation needs further investigation.…”

Neuroprotective Effect of Nosustrophine in a 3xTg Mouse Model of Alzheimer’s Disease

“…Therefore, in our study the neuroprotective effect of Nosustrophine treatment showed to be crucial on the maintenance of neurogenesis observed in the dentate gyrus of EB/3xTg-AD transgenic mice, suggesting a pivotal role of the brain derived peptides in the induction and regulation of neurogenesis through different mechanisms. Neurotrophic actions of brain-derived peptides are essential for the differentiation and early maturation of neuronal cell layers [ 37 , 38 ], triggers osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells [ 39 , 40 ], demonstrating its efficiency as a potential biosource of tissue regeneration. Therefore, similar beneficial effects were observed when Nosustrophine was supplemented in the diet of AD mouse models, demonstrating not only the cytoarchitecture maintenance of neurogenesis layers within the periventricular brain areas but also the reduction in the pathologic degenerative hallmarks of the disease.…”

Overview of Physical and Pharmacological Therapy in Enhancing Bone Regeneration Formation During Distraction Osteogenesis

“…FGFs play a significant role in tissue repair, angiogenesis and vascular permeability. Xu et al reported that PBE promoted osteogenic differentiation of rBMSCs, and their local treatment accelerated bone formation and consolidation in a rat DO model ( Xu et al, 2017a ). These findings indicate that PBE might be a promising bio-source to be utilized to promote new bone regeneration (due to it is extremely cost-effective and easily available).…”