Systemic and Local Administration of Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells Promotes Fracture Healing in Rats

Huang, Shuo; Xu, Liangliang; Zhang, Yifeng; Sun, Yuxin; Li, Gang

doi:10.3727/096368915x687219

Cited by 70 publications

(52 citation statements)

References 37 publications

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“…The disease is widely observed on a global scale, and is the primary cause of fractures and bone loss, and seriously threatens human health (1). The suppression of bone-forming ability is the main pathogenesis of the disease.…”

Section: Introductionmentioning

confidence: 99%

miR-214 suppresses the osteogenic differentiation of bone marrow-derived mesenchymal stem cells and these effects are mediated through the inhibition of the JNK and p38 pathways

Guo

Gao

et al. 2016

International Journal of Molecular Medicine

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In this study, we sought to investigate the expression of microRNA (miR)-214 on the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and explore the possible underlying mechanisms. We found that the overexpression of miR-214 effectively promoted the adipocyte differentiation of BMSCs in vitro, reduced alkaline phosphatase (ALP) activity and the gene expression of collagen type I (Col I), osteocalcin (OCN) and osteopontin (OPN) in the BMSCs. We further found that the overexpression of miR-214 suppressed the protein expression of fibroblast growth factor (FGF), phosphorylated c-Jun N-terminal kinase (p-JNK) and phosphorylated p38 (p-p38) in the BMSCs. The downregulation of miR-214 promoted the osteogenic differentiation of BMSCs, and increased ALP activity and Col I, OCN and OPN gene expression in the BMSCs. It also increased FGF p-JNK and p-p38 protein expression in the BMSCs. The use of JNK inhibitor (SP600125) enhanced the inhibitory effects of miR-214 overexpression on osteogenic differentiation, ALP activity, and Col I, OCN and OPN gene expression in the BMSCs. Lastly, the use of p38 inhibitor (SB202190) also enhanced the inhibitory effects of miR-214 overexpression on ALP activity, and Col I, OCN and OPN gene expression in the BMSCs. These results provide a mechanism responsible for the suppressive effects of miR-214 on the osteogenic differentiation of BMSCs involving the inhibition of the JNK and p38 pathways.

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Section: Introductionmentioning

confidence: 99%

miR-214 suppresses the osteogenic differentiation of bone marrow-derived mesenchymal stem cells and these effects are mediated through the inhibition of the JNK and p38 pathways

Guo

Gao

et al. 2016

International Journal of Molecular Medicine

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“…Systemic injection of MSCs has been used in the treatment of osteoporosis and fracture healing for many years [Huang et al, 2015]. Several factors are involved in order to achieve more successful results from cell therapy in bone healing.…”

Section: Systemic Injection Approachmentioning

confidence: 99%

Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence?

Oryan

Kamali²,

Moshiri³

et al. 2017

Cells Tissues Organs

292

204

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Healing and regeneration of bone injuries, particularly those that are associated with large bone defects, are a complicated process. There is growing interest in the application of osteoinductive and osteogenic growth factors and mesenchymal stem cells (MSCs) in order to significantly improve bone repair and regeneration. MSCs are multipotent stromal stem cells that can be harvested from many different sources and differentiated into a variety of cell types, such as preosteogenic chondroblasts and osteoblasts. The effectiveness of MSC therapy is dependent on several factors, including the differentiating state of the MSCs at the time of application, the method of their delivery, the concentration of MSCs per injection, the vehicle used, and the nature and extent of injury, for example. Tissue engineering and regenerative medicine, together with genetic engineering and gene therapy, are advanced options that may have the potential to improve the outcome of cell therapy. Although several in vitro and in vivo investigations have suggested the potential roles of MSCs in bone repair and regeneration, the mechanism of MSC therapy in bone repair has not been fully elucidated, the efficacy of MSC therapy has not been strongly proven in clinical trials, and several controversies exist, making it difficult to draw conclusions from the results. In this review, we update the recent advances in the mechanisms of MSC action and the delivery approaches in bone regenerative medicine. We will also review the most recent clinical trials to find out how MSCs may be beneficial for treating bone defects.

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“…Mesenchymal stromal cells (MSCs) have potentials for bone regeneration [1][2][3]. Previous reports indicated that MSCs could repair damaged tissue by replacing damaged cells [3].…”

Section: Introductionmentioning

confidence: 99%

Different Bone Healing Effects of Undifferentiated and Osteogenic Differentiated Mesenchymal Stromal Cell Sheets in Canine Radial Fracture Model

Yoon

Khan

Choi

et al. 2017

Tissue Eng Regen Med

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Cell sheets technology is being available for fracture healing. This study was performed to clarify bone healing mechanism of undifferentiated (UCS) and osteogenic (OCS) differentiated mesenchymal stromal cell (MSC) sheets in the fracture model of dogs. UCS and OCS were harvested at 10 days of culture. Transverse fractures at the radius of six beagle dogs were assigned into three groups (n = 4 in each group) i.e. UCS, OCS and control. The fractures were fixed with a 2.7 mm locking plate and six screws. Cell sheets were wrapped around the fracture site. Bones were harvested 8 weeks after operation, then scanned by micro-computed tomography (micro-CT) and analyzed histopathologically. The micro-CT revealed different aspects of bone regeneration among the groups. The percentages of external callus volume out of total bone volume in control, UCS, and OCS groups were 42.1, 13.0 and 4.9% (p \ 0.05) respectively. However, the percentages of limbs having connectivity of gaps were 25, 12.5 and 75% respectively. In histopathological assessments, OCS group showed well organized and mature woven bone with peripheral cartilage at the fracture site, whereas control group showed cartilage formation without bone maturation or ossification at the fracture site. Meanwhile, fracture site was only filled with fibrous connective tissue without endochondral ossification and bone formation in UCS group. It was suggested that the MSC sheets reduced the quantity of external callus, and OCS induced the primary bone healing.

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Systemic and Local Administration of Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells Promotes Fracture Healing in Rats

Cited by 70 publications

References 37 publications

miR-214 suppresses the osteogenic differentiation of bone marrow-derived mesenchymal stem cells and these effects are mediated through the inhibition of the JNK and p38 pathways

miR-214 suppresses the osteogenic differentiation of bone marrow-derived mesenchymal stem cells and these effects are mediated through the inhibition of the JNK and p38 pathways

Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence?

Different Bone Healing Effects of Undifferentiated and Osteogenic Differentiated Mesenchymal Stromal Cell Sheets in Canine Radial Fracture Model

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