scholarly journals Genetically Engineered-MSC Therapies for Non-unions, Delayed Unions and Critical-size Bone Defects

2019 ◽  
Vol 20 (14) ◽  
pp. 3430 ◽  
Author(s):  
Jaime Freitas ◽  
Susana Gomes Santos ◽  
Raquel Madeira Gonçalves ◽  
José Henrique Teixeira ◽  
Mário Adolfo Barbosa ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Animal Studies ◽  
Bone Repair ◽  
Critical Size ◽  
Clinical Problem ◽  
Cell Types ◽  
Bone Defects ◽  
Genetically Engineered ◽  
Beneficial Effects

The normal bone regeneration process is a complex and coordinated series of events involving different cell types and molecules. However, this process is impaired in critical-size/large bone defects, with non-unions or delayed unions remaining a major clinical problem. Novel strategies are needed to aid the current therapeutic approaches. Mesenchymal stem/stromal cells (MSCs) are able to promote bone regeneration. Their beneficial effects can be improved by modulating the expression levels of specific genes with the purpose of stimulating MSC proliferation, osteogenic differentiation or their immunomodulatory capacity. In this context, the genetic engineering of MSCs is expected to further enhance their pro-regenerative properties and accelerate bone healing. Herein, we review the most promising molecular candidates (protein-coding and non-coding transcripts) and discuss the different methodologies to engineer and deliver MSCs, mainly focusing on in vivo animal studies. Considering the potential of the MSC secretome for bone repair, this topic has also been addressed. Furthermore, the promising results of clinical studies using MSC for bone regeneration are discussed. Finally, we debate the advantages and limitations of using MSCs, or genetically-engineered MSCs, and their potential as promoters of bone fracture regeneration/repair.

scholarly journals Preliminary in Vivo Evaluation of Bone Healing in Critical Size Bone Defects Implanted with an Injectable Calcium Phosphate Bone Cement (Osteopaste)

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Che Nor Zarida Che Seman ◽  
Zamzuri Zakaria ◽  
Zunariah Buyong ◽  
Mohd Shukrimi Awang ◽  
Ahmad Razali Md Ralib @ Md Raghib
Keyword(s):  
Calcium Phosphate ◽  
Bone Cement ◽  
Bone Tissue ◽  
Bone Repair ◽  
Critical Size ◽  
Healing Process ◽  
Bone Defects ◽  
Calcium Phosphate Bone Cement ◽  
Rabbit Tibia

Introduction: A novel injectable calcium phosphate bone cement (osteopaste) has been developed. Its potential application in orthopaedics as a filler of bone defects has been studied. The biomaterial was composed of tetra-calcium phosphate (TTCP) and tricalcium phosphate (TCP) powder. The aim of the present study was to evaluate the healing process of osteopaste in rabbit tibia. Materials and method: The implantation procedure was carried out on thirty-nine of New Zealand white rabbits. The in vivo bone formation was investigated by either implanting the Osteopaste, Jectos or MIIG – X3 into a critical size defect (CSD) model in the proximal tibial metaphysis. CSD without treatment served as negative control. After 1 day, 6 and 12 weeks, the rabbits were euthanized, the bone were harvested and subjected for analysis. Results: Radiological images and histological sections revealed integration of implants with bone tissue with no signs of graft rejection. There was direct contact between osteopaste material and host bone. The new bone was seen bridging the defect. Conclusion: The result showed that Osteopaste could be a new promising biomaterial for bone repair and has a potential in bone tissue engineering.

scholarly journals Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

2017 ◽  
Vol 8 ◽  
pp. 204173141771207 ◽  
Author(s):  
Mathieu Maisani ◽  
Daniele Pezzoli ◽  
Olivier Chassande ◽  
Diego Mantovani
Keyword(s):  
Bone Regeneration ◽  
Bone Tissue ◽  
Bone Repair ◽  
Critical Issue ◽  
Bone Defects ◽  
Bone Tissue Regeneration ◽  
Differentiation Potential ◽  
Promising Alternative

Tissue engineering is a promising alternative to autografts or allografts for the regeneration of large bone defects. Cell-free biomaterials with different degrees of sophistication can be used for several therapeutic indications, to stimulate bone repair by the host tissue. However, when osteoprogenitors are not available in the damaged tissue, exogenous cells with an osteoblast differentiation potential must be provided. These cells should have the capacity to colonize the defect and to participate in the building of new bone tissue. To achieve this goal, cells must survive, remain in the defect site, eventually proliferate, and differentiate into mature osteoblasts. A critical issue for these engrafted cells is to be fed by oxygen and nutrients: the transient absence of a vascular network upon implantation is a major challenge for cells to survive in the site of implantation, and different strategies can be followed to promote cell survival under poor oxygen and nutrient supply and to promote rapid vascularization of the defect area. These strategies involve the use of scaffolds designed to create the appropriate micro-environment for cells to survive, proliferate, and differentiate in vitro and in vivo. Hydrogels are an eclectic class of materials that can be easily cellularized and provide effective, minimally invasive approaches to fill bone defects and favor bone tissue regeneration. Furthermore, by playing on their composition and processing, it is possible to obtain biocompatible systems with adequate chemical, biological, and mechanical properties. However, only a good combination of scaffold and cells, possibly with the aid of incorporated growth factors, can lead to successful results in bone regeneration. This review presents the strategies used to design cellularized hydrogel-based systems for bone regeneration, identifying the key parameters of the many different micro-environments created within hydrogels.

scholarly journals Mesenchymal Stem Cells as a Potent Cell Source for Bone Regeneration

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Elham Zomorodian ◽  
Mohamadreza Baghaban Eslaminejad
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Bone Repair ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
Bone Defects ◽  
Bone Transplantation ◽  
Allogenic Bone

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.

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

2017 ◽  
Vol 204 (2) ◽  
pp. 59-83 ◽  
Author(s):  
Ahmad Oryan ◽  
Amir Kamali ◽  
Ali Moshiri ◽  
Mohamadreza Baghaban Eslaminejad
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Regenerative Medicine ◽  
Bone Repair ◽  
Cell Types ◽  
Bone Defects ◽  
Time Of Application

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.

scholarly journals Cytolytic viruses as potential anti-cancer agents

2002 ◽  
Vol 83 (3) ◽  
pp. 491-502 ◽  
Author(s):  
Christopher J. A. Ring
Keyword(s):  
Animal Studies ◽  
Virus Disease ◽  
Cell Types ◽  
Genetically Engineered ◽  
Tumour Cells ◽  
Oncolytic Viruses ◽  
Host Cells ◽  
Genetic Vectors ◽  
Simplex Virus

The resistance of cancers to conventional therapies has inspired the search for novel strategies. One such approach, namely gene therapy, is based upon the introduction of genes such as those encoding suicide proteins, tumour suppressor proteins or cytokines into tumour cells by means of a genetic vector. The efficiency with which viruses transfer their genes from one host cell to another has led to the widespread use of viruses as genetic vectors. For safety reasons, such virus vectors are generally replication-defective but, unfortunately, this has limited the efficacy of treatment by restricting the number of cells to which the therapeutic gene is delivered. For this reason, the use of replication-competent viruses has been proposed, since virus replication would be expected to lead to amplification and spread of the therapeutic genes in vivo. The replication of many viruses results in lysis of the host cells. This inherent cytotoxicity, together with the efficiency with which viruses can spread from one cell to another, has inspired the notion that replication-competent viruses could be exploited for cancer treatment. Some viruses have been shown to replicate more efficiently in transformed cells but it is unlikely that such examples will exhibit a high enough degree of tumour selectivity, and hence safety, for the treatment of patients. Our increasing knowledge of the pathogenesis of virus disease and the ability to manipulate specific regions of viral genomes have allowed the construction of viruses that are attenuated in normal cells but retain their ability to lyse tumour cells. Such manipulations have included modifying the ability of viruses to bind to, or replicate in, particular cell types, while others have involved the construction of replication-competent viruses encoding suicide proteins or cytokines. Naturally occurring or genetically engineered oncolytic viruses based upon adenovirus, herpes simplex virus, Newcastle disease virus, poliovirus, vesicular stomatitis virus, weasles virus and reovirus have been described. The results of animal studies are encouraging and a number of viruses are now being evaluated in clinical trials.

Decellularized bone extracellular matrix in skeletal tissue engineering

2020 ◽  
Vol 48 (3) ◽  
pp. 755-764
Author(s):  
Benjamin B. Rothrauff ◽  
Rocky S. Tuan
Keyword(s):  
Tissue Engineering ◽  
Bone Regeneration ◽  
Tissue Regeneration ◽  
Animal Studies ◽  
Tumor Resection ◽  
Regenerative Capacity ◽  
Skeletal Tissue ◽  
Large Bone

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.

Regeneration of Bone Defects Using Bioactive Glass Combined with Adipose-derived Mesenchymal Stem Cells. An experimental in vivo study

2019 ◽  
Vol 70 (6) ◽  
pp. 1983-1987
Author(s):  
Cristian Trambitas ◽  
Anca Maria Pop ◽  
Alina Dia Trambitas Miron ◽  
Dorin Constantin Dorobantu ◽  
Flaviu Tabaran ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bioactive Glass ◽  
Bone Repair ◽  
Bone Defects ◽  
Calvarial Bone ◽  
Specific Protocol ◽  
Repair Mechanisms ◽  
Male Wistar Rats

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.

Sign in / Sign up

Export Citation Format

Share Document