scholarly journals Improvement of the ability of bone repair by reducing the aging degree of mesenchymal stem cell population by Senolytic drugs

2021 ◽  
Vol 271 ◽  
pp. 03015
Author(s):  
Jia Liu ◽  
Lian He ◽  
Peng Zhou ◽  
Danna Chen

In order to study the effects of Senolytic drugs dasatinib and quercetin on the aging of mesenchymal stem cells (MSCs) and explore the application of young MSCs in repairing bone defects, the cultured and identified MSCs were treated with dasatinib and quercetin, counting the number of passage times, and the senescence of cells was evaluated by high-content screening microscopy. The 4th-passage MSCs rejuvenated with Senolytic drugs were transplanted into bone defect model rabbits, and X-ray examination was performed 12 weeks after surgery. The results showed that Senolytic drugs reduced the senility of MSCs and improved the ability of bone repair.

2019 ◽  
Vol 70 (6) ◽  
pp. 1983-1987
Author(s):  
Cristian Trambitas ◽  
Anca Maria Pop ◽  
Alina Dia Trambitas Miron ◽  
Dorin Constantin Dorobantu ◽  
Flaviu Tabaran ◽  
...  

Large bone defects are a medical concern as these are often unable to heal spontaneously, based on the host bone repair mechanisms. In their treatment, bone tissue engineering techniques represent a promising approach by providing a guide for osseous regeneration. As bioactive glasses proved to have osteoconductive and osteoinductive properties, the aim of our study was to evaluate by histologic examination, the differences in the healing of critical-sized calvarial bone defects filled with bioactive glass combined with adipose-derived mesenchymal stem cells, compared to negative controls. We used 16 male Wistar rats subjected to a specific protocol based on which 2 calvarial bone defects were created in each animal, one was filled with Bon Alive S53P4 bioactive glass and adipose-derived stem cells and the other one was considered control. At intervals of one week during the following month, the animals were euthanized and the specimens from bone defects were histologically examined and compared. The results showed that this biomaterial was biocompatible and the first signs of osseous healing appeared in the third week. Bone Alive S53P4 bioactive glass could be an excellent bone substitute, reducing the need of bone grafts.


2020 ◽  
Author(s):  
Xue-Cheng Sun ◽  
Hu Wang ◽  
Jian-Hui Li ◽  
Dan Zhang ◽  
Xu Ma ◽  
...  

Abstract Background: Alveolar cleft is a kind of cleft lip and palate, which seriously affects the physical and mental health of patients. In this study , the model of the alveolar cleft phenotype was established in rabbits to evaluate the effect of bone collagen particles combined with human umbilical cord mesenchymal stem cells (HUC-MSCs) on the repair of alveolar cleft bone defects. Methods : The model of alveolar clefts in rabbits was established by removing the incisors on the left side of the upper jaw. Bone collagen particles combined with hUC-MSCs were implanted in the defect area. Blood biochemical analysis was performed after 3 months. Skull tissues were harvested for gross observation, and micro-focus computerized tomography (micro-CT) analysis. Tissues were harvested for histological and immunohistochemical staining. The experiments were repeated 6 months after surgery. Results: The bone collagen particles and HUC-MSCs have good biological safety. In addition, both can promote the regeneration of incisor. Bone collagen particles combined with hUC-MSCs were much better than those used alone in inducing bone repair and regeneration. Conclusions: The method of HUC-MSCs combined with bone collagen particle material to fill a bone defect site is simple, rapid and suitable for the treatment of alveolar cleft bone defects.


Author(s):  
GG Franco ◽  
BW Minto ◽  
LP Coelho ◽  
PF Malard ◽  
ER Carvalho ◽  
...  

This study aims to evaluate the effect of autologous adipose-derived mesenchymal stem cells (AAD-MSC), with and without synthetic absorbable hydroxyapatite (HAP-91), on the bone regeneration in rabbits. Thirty-four female white New Zealand rabbits were submitted to a 10 mm distal diaphyseal radius ostectomy, divided into 3 experimental groups according to the treatment established. The bone gap was filled with 0.15 ml of a 0.9% saline solution containing two million AAD-MSC (G1), or AAD-MSC associated with HAP-91 (G2). The control group (CG) received only 0.15 ml of the 0.9% saline solution. Radiographs were made post-operatively, and after 15, 30, 45 and 90 days. Fifty percent of the samples were submitted to a histological examination at 45 days and the remaining ones at 90 days post-operatively. Radiographically, the periosteal reaction, bone callus volume and bone bridge quality were superior in G2 (P < 0.05). Histologically, the bone repair was faster and more efficient in G1 at 45 days (P < 0.05). In conclusion, AAD-MSC improved the regeneration on the experimentally induced bone defects in rabbits; however, the use of hydroxyapatite requires caution given the granulomatous reaction produced in the species.


2020 ◽  
Vol 21 (16) ◽  
pp. 5816
Author(s):  
Kar Wey Yong ◽  
Jane Ru Choi ◽  
Jean Yu Choi ◽  
Alistair C. Cowie

Large bone defects are a major health concern worldwide. The conventional bone repair techniques (e.g., bone-grafting and Masquelet techniques) have numerous drawbacks, which negatively impact their therapeutic outcomes. Therefore, there is a demand to develop an alternative bone repair approach that can address the existing drawbacks. Bone tissue engineering involving the utilization of human mesenchymal stem cells (hMSCs) has recently emerged as a key strategy for the regeneration of damaged bone tissues. However, the use of tissue-engineered bone graft for the clinical treatment of bone defects remains challenging. While the role of mechanical loading in creating a bone graft has been well explored, the effects of mechanical loading factors (e.g., loading types and regime) on clinical outcomes are poorly understood. This review summarizes the effects of mechanical loading on hMSCs for bone tissue engineering applications. First, we discuss the key assays for assessing the quality of tissue-engineered bone grafts, including specific staining, as well as gene and protein expression of osteogenic markers. Recent studies of the impact of mechanical loading on hMSCs, including compression, perfusion, vibration and stretching, along with the potential mechanotransduction signalling pathways, are subsequently reviewed. Lastly, we discuss the challenges and prospects of bone tissue engineering applications.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Long Chen ◽  
Wei Luo ◽  
Yuanzheng Wang ◽  
Xiongbo Song ◽  
Senlei Li ◽  
...  

Abstract Background One of the greatest challenges for tissue-engineered bone is the low survival rate of locally grafted cells. The cell homing technology can effectively increase the number of these grafted cells, therefore, enhancing the repair of bone defects. Here we explore the effect of fucosylation modification on the directional homing of bone marrow mesenchymal stem cells (BMSCs) and their ability to repair bone defects. Results Glycosylated BMSCs expressed high levels of the Sialyl Lewis-X (sLeX) antigen, which enabled the cells to efficiently bind to E- and P-selectins and to home to bone defect sites in vivo. Micro-CT and histological staining results confirmed that mice injected with FuT7-BMSCs showed an improved repair of bone defects compared to unmodified BMSCs. Conclusions The glycosylation modification of BMSCs has significantly enhanced their directional homing ability to bone defect sites, therefore, promoting bone repair. Our results suggest that glycosylation-modified BMSCs can be used as the source of the cells for the tissue-engineered bone and provide a new approach for the treatment of bone defects. Graphic Abstract


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Elham Zomorodian ◽  
Mohamadreza Baghaban Eslaminejad

While small bone defects heal spontaneously, large bone defects need surgical intervention for bone transplantation. Autologous bone grafts are the best and safest strategy for bone repair. An alternative method is to use allogenic bone graft. Both methods have limitations, particularly when bone defects are of a critical size. In these cases, bone constructs created by tissue engineering technologies are of utmost importance. Cells are one main component in the manufacture of bone construct. A few cell types, including embryonic stem cells (ESCs), adult osteoblast, and adult stem cells, can be used for this purpose. Mesenchymal stem cells (MSCs), as adult stem cells, possess characteristics that make them good candidate for bone repair. This paper discusses different aspects of MSCs that render them an appropriate cell type for clinical use to promote bone regeneration.


2017 ◽  
Vol 204 (2) ◽  
pp. 59-83 ◽  
Author(s):  
Ahmad Oryan ◽  
Amir Kamali ◽  
Ali Moshiri ◽  
Mohamadreza Baghaban Eslaminejad

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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