Osteogenesis and angiogenesis are simultaneously enhanced in BMP2-/VEGF-transfected adipose stem cells through activation of the YAP/TAZ signaling pathway

2019 ◽  
Vol 7 (11) ◽  
pp. 4588-4602 ◽  
Author(s):  
Eugene Lee ◽  
Ji-Yun Ko ◽  
Juyoung Kim ◽  
Jeong-Won Park ◽  
Songhee Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathway ◽  
Malignant Tumors ◽  
Bone Defects ◽  
Great Difficulty ◽  
Adipose Stem Cells ◽  
Large Bone ◽  
Large Bone Defects

While bone has the capability to heal itself, there is a great difficulty in reconstituting large bone defects created by heavy trauma or the resection of malignant tumors.

scholarly journals Methyltransferase-like protein 7A (METTL7A) promotes cell survival and osteogenic differentiation under metabolic stress

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Eugene Lee ◽  
Ju-young Kim ◽  
Tae-Kyung Kim ◽  
Seo-Young Park ◽  
Gun-Il Im
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Survival ◽  
Osteogenic Differentiation ◽  
Cell Transplantation ◽  
Methylation Status ◽  
Bone Defects ◽  
Large Bone ◽  
Large Bone Defects

AbstractWhile bone has an inherent capacity to heal itself, it is very difficult to reconstitute large bone defects. Regenerative medicine, including stem cell implantation, has been studied as a novel solution to treat these conditions. However, when the local vascularity is impaired, even the transplanted cells undergo rapid necrosis before differentiating into osteoblasts and regenerating bone. Thus, to increase the effectiveness of stem cell transplantation, it is quintessential to improve the viability of the implanted stem cells. In this study, given that the regulation of glucose may hold the key to stem cell survival and osteogenic differentiation, we investigated the molecules that can replace the effect of glucose under ischemic microenvironment of stem cell transplantation in large bone defects. By analyzing differentially expressed genes under glucose-supplemented and glucose-free conditions, we explored markers such as methyltransferase-like protein 7A (METTL7A) that are potentially related to cell survival and osteogenic differentiation. Overexpression of METTL7A gene enhanced the osteogenic differentiation and viability of human bone marrow stem cells (hBMSCs) in glucose-free conditions. When the in vivo effectiveness of METTL7A-transfected cells in bone regeneration was explored in a rat model of critical-size segmental long-bone defect, METTL7A-transfected hBMSCs showed significantly better regenerative potential than the control vector-transfected hBMSCs. DNA methylation profiles showed a large difference in methylation status of genes related to osteogenesis and cell survival between hBMSCs cultured in glucose-supplemented condition and those cultured in glucose-free condition. Interestingly, METTL7A overexpression altered the methylation status of related genes to favor osteogenic differentiation and cell survival. In conclusion, it is suggested that a novel factor METTL7A enhances osteogenic differentiation and viability of hBMSCs by regulating the methylation status of genes related to osteogenesis or survival.

scholarly journals Healing of Large Segmental Bone Defect after Implantation of Autogenous Cancellous Bone Graft in Comparison to Hydroxyapatite and 0.5% Collagen Scaffold Combined with Mesenchymal Stem Cells

2010 ◽  
Vol 79 (4) ◽  
pp. 607-612 ◽  
Author(s):  
Alois Nečas ◽  
Pavel Proks ◽  
Lucie Urbanová ◽  
Robert Srnec ◽  
Ladislav Stehlík ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Graft ◽  
Cancellous Bone ◽  
Bone Defects ◽  
Cancellous Bone Graft ◽  
Collagen Group ◽  
Significant Difference ◽  
Large Bone ◽  
Large Bone Defects

At present, attention is focused on research into possibilities of healing large bone defects by the method of mini-invasive osteosynthesis, using implantation of biomaterials and mesenchymal stem cells (MSCs). This study evaluates the healing of segmental femoral defects in miniature pigs based on the radiological determination of the callus: cortex ratio at 16 weeks after ostectomy. The size of the formed callus was significantly larger (p < 0.05) in animals after transplantation of an autogenous cancellous bone graft (group A, callus : cortex ratio of 1.77 ± 0.33) compared to animals after transplantation of cylindrical scaffold from hydroxyapatite and 0.5% collagen (group S, callus : cortex ratio of 1.08 ± 0.13), or in animals after transplantation of this scaffold seeded with MSCs (group S + MSCs, callus: cortex ratio of 1.15 ± 0.18). No significant difference was found in the size of callus between animals of group S and animals of group S + MSCs. Unlike a scaffold in the shape of the original bone column, a freely placed autogenous cancellous bone graft may allow the newly formed tissue to spread more to the periphery of the ostectomy defect. Implanted cylindrical scaffolds (with and without MSCs) support callus formation directly in the center of original bone column in segmental femoral ostectomy, and can be successfully used in the treatment of large bone defects.

Study of the Effect of Mechanical Loading on Cell Cultures in Bone Tissue Engineering

2012 ◽  
Author(s):  
Magali Cruel ◽  
Morad Bensidhoum ◽  
Laure Sudre ◽  
Guillaume Puel ◽  
Virginie Dumas ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Bone Defects ◽  
Improved Design ◽  
Large Bone ◽  
Large Bone Defects

Bone tissue engineering currently represents one of the most interesting alternatives to autologous transplants and their drawbacks in the treatment of large bone defects. Mesenchymal stem cells are used to build new bone in vitro in a bioreactor. Their stimulation and our understanding of the mechanisms of mechanotransduction need to be improved in order to optimize the design of bioreactors. In this study, several geometries of bioreactor were analyzed experimentally and biological results were linked with numerical simulations of the flow inside the bioreactor. These results will constitute a base for an improved design of the existing bioreactor.

Engineering Bone with Mesenchymal Stem Cells: Challenges and Obstacles

2021 ◽  
Author(s):  
Guotian Luo ◽  
Giuliana E. Salazar-Noratto ◽  
Esther Potier ◽  
Hervé Petite
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Metabolic Regulation ◽  
Critical Role ◽  
Bone Defects ◽  
Massive Cell Death ◽  
Scaffold Degradation ◽  
Large Bone ◽  
Post Implantation ◽  
Large Bone Defects

Repair and reconstruction of large bone defects remain a significant challenge. Cell construct, containing mesenchymal stem cells (MSCs) and scaffold, is a promising strategy for addressing and treating major orthopedic clinical conditions. However, the design of an ideal cell construct for engineering bone faces two critical challenges (i) matching the scaffold degradation rate to that of new bone formation and (ii) preventing the massive cell death post-implantation (caused by disruption of oxygen and nutrient supply). We will hereby primarily focus on the challenge of survival of MSCs post-implantation. Increasing evidence indicates that metabolic regulation plays a critical role in cell fate and functions. In cell metabolism, glucose is considered the major metabolic substrate to produce ATP via glycolysis when the availability of oxygen is limited. In this paper, we delineate the essential roles of glucose on MSC survival. We aim to provide a different perspective which highlights the importance of considering glucose in the development of tissue engineering strategies in order to improve the efficiency of MSC-based cell constructs in the repair of large bone defects.

Effects of mesenchymal stem cells treated with BMP-2 and VEGF on regeneration of large bone defects

2014 ◽  
Vol 15 (1) ◽  
pp. 24-31 ◽  
Author(s):  
Jae Kyong Kim ◽  
Se Eun Kim ◽  
Kyung Mi Shim ◽  
Chun-Sik Bae ◽  
Seok Hwa Choi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Defects ◽  
Large Bone ◽  
Large Bone Defects

scholarly journals Exploring the Mechanism of Total Flavonoids of Drynariae Rhizoma to Improve Large Bone Defects by Network Pharmacology and Experimental Assessment

2021 ◽  
Vol 12 ◽  
Author(s):  
Weipeng Sun ◽  
Minying Li ◽  
Lei Xie ◽  
Zhexing Mai ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Bone Defects ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Network Pharmacology ◽  
Dosage Group ◽  
Active Ingredients ◽  
Large Bone ◽  
Large Bone Defects

Drynariae Rhizoma (DR) has been demonstrated to be effective in promoting fracture healing in clinical use. In the study, we tried to predicate potential signaling pathways and active ingredients of DR via network pharmacology, uncover its regulation mechanism to improve large bone defects by in vivo and in vitro experiment. We total discovered 18 potential active ingredients such as flavonoids and 81 corresponding targets, in which mitogen-activated protein kinase (MAPK) signaling pathway has the highest correlation with bone defects in pathway and functional enrichment analysis. Therefore, we hypothesized that flavonoids in DR improve large bone defects by activating MAPK signaling pathway. Animal experiments were carried out and all rats randomly divided into TFDR low, medium, and high dosage group, model group and control group. 12 weeks after treatment, according to X-ray and Micro-CT, TFDR medium dosage group significantly promote new bone mineralization compared with other groups. The results of HE and Masson staining and in vitro ALP level of BMSC also demonstrated the formation of bone matrix and mineralization in the TFDR groups. Also, angiographic imaging suggested that flavonoids in DR promoting angiogenesis in the defect area. Consistently, TFDR significantly enhanced the expression of BMP-2, RUNX-2, VEGF, HIF-1 in large bone defect rats based on ELISA and Real-Time PCR. Overall, we not only discover the active ingredients of DR in this study, but also explained how flavonoids in DR regulating MAPK signaling pathway to improve large bone defects.

scholarly journals Clinical Applications of Cell-Scaffold Constructs for Bone Regeneration Therapy

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2687
Author(s):  
Venkata Suresh Venkataiah ◽  
Yoshio Yahata ◽  
Akira Kitagawa ◽  
Masahiko Inagaki ◽  
Yusuke Kakiuchi ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Bone Tissue Engineering ◽  
Bone Regeneration ◽  
Bone Tissue ◽  
Bone Defects ◽  
Significant Loss ◽  
Osteogenic Potential ◽  
Large Bone ◽  
Large Bone Defects

Bone tissue engineering (BTE) is a process of combining live osteoblast progenitors with a biocompatible scaffold to produce a biological substitute that can integrate into host bone tissue and recover its function. Mesenchymal stem cells (MSCs) are the most researched post-natal stem cells because they have self-renewal properties and a multi-differentiation capacity that can give rise to various cell lineages, including osteoblasts. BTE technology utilizes a combination of MSCs and biodegradable scaffold material, which provides a suitable environment for functional bone recovery and has been developed as a therapeutic approach to bone regeneration. Although prior clinical trials of BTE approaches have shown promising results, the regeneration of large bone defects is still an unmet medical need in patients that have suffered a significant loss of bone function. In this present review, we discuss the osteogenic potential of MSCs in bone tissue engineering and propose the use of immature osteoblasts, which can differentiate into osteoblasts upon transplantation, as an alternative cell source for regeneration in large bone defects.

scholarly journals Factors related to large bone defects of bipolar lesions and a high number of instability episodes with anterior glenohumeral instability

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Noboru Matsumura ◽  
Kazuya Kaneda ◽  
Satoshi Oki ◽  
Hiroo Kimura ◽  
Taku Suzuki ◽  
...  
Keyword(s):  
Humeral Head ◽  
Glenohumeral Joint ◽  
Three Dimensional ◽  
Clinical Results ◽  
Bone Defects ◽  
Symptom Duration ◽  
Glenohumeral Instability ◽  
Explanatory Variables ◽  
Large Bone ◽  
Large Bone Defects

Abstract Background Significant bone defects are associated with poor clinical results after surgical stabilization in cases of glenohumeral instability. Although multiple factors are thought to adversely affect enlargement of bipolar bone loss and increased shoulder instability, these factors have not been sufficiently evaluated. The purpose of this study was to identify the factors related to greater bone defects and a higher number of instability episodes in patients with glenohumeral instability. Methods A total of 120 consecutive patients with symptomatic unilateral instability of the glenohumeral joint were retrospectively reviewed. Three-dimensional surface-rendered/registered models of bilateral glenoids and proximal humeri from computed tomography data were matched by software, and the volumes of bone defects identified in the glenoid and humeral head were assessed. After relationships between objective variables and explanatory variables were evaluated using bivariate analyses, factors related to large bone defects in the glenoid and humeral head and a high number of total instability episodes and self-irreducible dislocations greater than the respective 75th percentiles were evaluated using logistic regression analyses with significant variables on bivariate analyses. Results Larger humeral head defects (P < .001) and a higher number of total instability episodes (P = .032) were found to be factors related to large glenoid defects. On the other hand, male sex (P = .014), larger glenoid defects (P = .015), and larger number of self-irreducible dislocations (P = .027) were related to large humeral head bone defects. An increased number of total instability episodes was related to longer symptom duration (P = .001) and larger glenoid defects (P = .002), and an increased number of self-irreducible dislocations was related to larger humeral head defects (P = .007). Conclusions Whereas this study showed that bipolar lesions affect the amount of bone defects reciprocally, factors related to greater bone defects differed between the glenoid and the humeral head. Glenoid defects were related to the number of total instability episodes, whereas humeral head defects were related to the number of self-irreducible dislocations.

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