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 ◽  
...  
2010 ◽  
Vol 79 (4) ◽  
pp. 607-612 ◽  
Author(s):  
Alois Nečas ◽  
Pavel Proks ◽  
Lucie Urbanová ◽  
Robert Srnec ◽  
Ladislav Stehlík ◽  
...  

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.


Author(s):  
Magali Cruel ◽  
Morad Bensidhoum ◽  
Laure Sudre ◽  
Guillaume Puel ◽  
Virginie Dumas ◽  
...  

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.


Author(s):  
Guotian Luo ◽  
Giuliana E. Salazar-Noratto ◽  
Esther Potier ◽  
Hervé Petite

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.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Eugene Lee ◽  
Ju-young Kim ◽  
Tae-Kyung Kim ◽  
Seo-Young Park ◽  
Gun-Il Im

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.


2019 ◽  
Vol 7 (11) ◽  
pp. 4588-4602 ◽  
Author(s):  
Eugene Lee ◽  
Ji-Yun Ko ◽  
Juyoung Kim ◽  
Jeong-Won Park ◽  
Songhee Lee ◽  
...  

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.


Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2687
Author(s):  
Venkata Suresh Venkataiah ◽  
Yoshio Yahata ◽  
Akira Kitagawa ◽  
Masahiko Inagaki ◽  
Yusuke Kakiuchi ◽  
...  

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.


2018 ◽  
Vol 55 (4) ◽  
pp. 691-695
Author(s):  
Tudor Sorin Pop ◽  
Anca Maria Pop ◽  
Alina Dia Trambitas Miron ◽  
Klara Brinzaniuc ◽  
Simona Gurzu ◽  
...  

The use of collagen scaffolds and stem cells for obtaining a tissue-engineering complex has been an important concept in promoting repair and regeneration of the bone tissue. Such units represent important steps in the development of an ideal scaffold-cell complex that would sustain new bone apposition. The aim of our study was to perform a histologic evaluation of the healing of critical-sized bone defects, using a biologic collagen scaffold with adipose-derived mesenchymal stem cells, in comparison to negative controls created in the adjacent bone. We used 16 Wistar rats and according to the study design 2 calvarial bone defects were created in each animal, one was filled with collagen seeded with adipose-derived stem cells and the other one was considered negative control. During the following month, at weekly intervals, the animals were euthanized and the specimens from bone defects were histologically evaluated. The results showed that these scaffolds were highly biocompatible as only moderate inflammation no rejection reactions were observed. Furthermore, the first signs of osseous healing appeared after two weeks accompanied by angiogenesis. Collagen scaffolds seeded with adipose-derived mesenchymal stem cells can be considered a promising treatment option in bone regeneration of large defects.


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