In vitro augmentation of mesenchymal stem cells viability in stressful microenvironments : In vitro augmentation of mesenchymal stem cells viability (original) (raw)
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Critical Reviews in Eukaryotic Gene Expression, 2015
Cancer is a major health problem in the world, and scientists seek innovative treatment strategies with higher efficacy and lower toxicity than the existing therapeutic agents. In this way, stem cell researchers try to reveal new pathways that will eventually benefit patients. Stem cell research has proven that mesenchymal stem cells (MSCs) possess anticancer activities, and their protein-rich secretome showed similar effects. MSCs also secrete cytokines that play an active role in healing and regeneration processes. Because of their known plasticity, MSCs display a variety of characteristics and functions in different environments, depending on their interactions with various cell types and tissues. Therefore, we hypothesize that MSC therapy in combination with anticancer medicines can potentiate cytotoxic effects on cancer cells. In addition, because of their regenerative capacity, MSCs can protect normal tissues from adverse cytotoxic drug reactions. They may also help rescue injured tissues from these toxic damages or systemic pathological events that occur during cancer treatment. MSC therapy may double the beneficial effects on cancer and normal cells. As our knowledge of systems biology and biotechnological methodology is progressing, this idea can move forward as a treatment option.
Biologics : targets & therapy, 2008
The therapeutic utilization of stem cells has been ongoing for several decades, principally in the form of bone marrow (BM) transplants to treat various hematological disorders and other immune-related diseases. More recently, stem cells have been examined as a potential therapy for a multitude of other diseases and disorders, many of which are currently untreatable. One consideration that poses a formidable task for the successful clinical application of stem cells in new disease models is the impact of the host tissue microenvironment on the desired therapeutic outcome. In vitro, stem cells exist in surroundings directly controllable by the researcher to produce the desired cellular behavior. In vivo, the transplanted cells are exposed to a dynamic host microenvironment laden with soluble mediators and immunoreactive cells. In this review, we focus on the possible contribution by microenvironmental factors, and how these influences can be overcome in therapies utilizing mesenchyma...
Mesenchymal Stem Cells and Pathotropism: Regenerative Potential and Safety Concerns
River Publishers eBooks, 2022
Mesenchymal Stem cells (MSCs) are ubiquitously expressed in several organs, but the major sites in adults are bone marrow and adipose tissue. MSCs can form several cells belonging to all germ layers, such as neurons and cardiomyocytes. MSCs have the potential to be used in cell therapy for many clinical problems, e.g., tissue regeneration, replacement, and to suppress inflammatory processes. MSCs are attractive due to reduced ethical concerns, ease in expansion and ability to be used as 'off-the-shelf' cells. MSCs can be indicated for clinical disorders due to their homing to regions of high cytokines such as tissue insult. This process is generally referred as pathotropism. MSCs have been placed in numerous clinical trials. Thus far, there is no evidence of safety concerns. Besides transplantation of hematopoietic stem cells, treatments with other stem cells are relatively recent. Thus, MSC therapy requires strict monitoring for safety issues. The pathotropic effect of MSCs allows these cells to home to tumors. This property led to the use of MSCs as cellular vehicle for drugs. A major concern of using MSCs in regenerative medicine is their ability to protect and support tumor growth. This chapter focuses on the potential safety concerns of using MSCs. This issue is particularly important if the recipient of stem cells has an undiagnosed tumor or is in cancer remission.
World journal of stem cells, 2009
Stem cell therapy is not a new field, as indicated by the success of hematopoietic stem cell reconstitution for various hematological malignancies and immune-mediated disorders. In the case of tissue repair, the major issue is whether stem cells should be implanted, regardless of the type and degree of injury. Mesenchymal stem cells have thus far shown evidence of safety, based on numerous clinical trials, particularly for immune-mediated disorders. The premise behind these trials is to regulate the stimulatory immune responses negatively. To apply stem cells for other disorders, such as acute injuries caused by insults from surgical trauma and myocardial infarction, would require other scientific considerations. This does not imply that such injuries are not accompanied by immune responses. Indeed, acute injuries could accompany infiltration of immune cells to the sites of injuries. The implantation of stem cells within a milieu of inflammation will establish an immediate crosstalk...
Mesenchymal stem cells and their microenvironment
Frontiers in Bioscience, 2011
2. Definition of Mesenchymal Stem Cells (MSC) 3. Definition of the stem cell niche 4. What is the stem cell niche for MSC? 5. Conditions that support MSC self-renewal versus differentiation 6. The effect of the extracellular matrix (ECM) on MSC 7. MSC and tissue damage 8. Contribution of MSCs to the HSC niche 9. MSCs and cancer 10. Acknowledgement 11. References
The life and fate of mesenchymal stem cells
Frontiers in immunology, 2014
Mesenchymal stem cells (MSC) are present throughout the body and are thought to play a role in tissue regeneration and control of inflammation. MSC can be easily expanded in vitro and their potential as a therapeutic option for degenerative and inflammatory disease is therefore intensively investigated. Whilst it was initially thought that MSC would replace dysfunctional cells and migrate to sites of injury to interact with inflammatory cells, experimental evidence indicates that the majority of administered MSC get trapped in capillary networks and have a short life span. In this review, we discuss current knowledge on the migratory properties of endogenous and exogenous MSC and confer on how culture-induced modifications of MSC may affect these properties. Finally, we will discuss how, despite their limited survival, administered MSC can bring about their therapeutic effects.
Mesenchymal stem cells and their use in therapy: What has been achieved?
Differentiation, 2013
The considerable therapeutic potential of human multipotent mesenchymal stromal cells or mesenchymal stem cells (MSCs) has generated increasing interest in a wide variety of biomedical disciplines. Nevertheless, researchers report studies on MSCs using different methods of isolation and expansion, as well as different approaches to characterize them; therefore, it is increasingly difficult to compare and contrast study outcomes. To begin to address this issue, the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy proposed minimal criteria to define human MSCs. First, MSCs must be plastic-adherent when maintained in standard culture conditions (a minimal essential medium plus 20% fetal bovine serum). Second, MSCs must express CD105, CD73 and CD90, and MSCs must lack expression of CD45, CD34, CD14 or CD11b, CD79a or CD19 and HLA-DR surface molecules. Third, MSCs must differentiate into osteoblasts, adipocytes and chondroblasts in vitro. MSCs are isolated from many adult tissues, in particular from bone marrow and adipose tissue. Along with their capacity to differentiate and transdifferentiate into cells of different lineages, these cells have also generated great interest for their ability to display immunomodulatory capacities. Indeed, a major breakthrough was the finding that MSCs are able to induce peripheral tolerance, suggesting that they may be used as therapeutic tools in immunemediated disorders. Although no significant adverse events have been reported in clinical trials to date, all interventional therapies have some inherent risks. Potential risks for undesirable events, such as tumor development, that might occur while using these stem cells for therapy must be taken into account and contrasted against the potential benefits to patients.
Mesenchymal stem cells, cancer challenges and new directions
Therapeutic use of multipotent mesenchymal stromal stem cells (MSC) is a promising venue for a large number of degenerative diseases and cancer. Their availability from many different adult tissues, ease of expansion in culture, the ability to avoid immune rejection and their homing ability, are some of the properties of MSCs that make them a great resource for therapy. However, the challenges and risks for cell-based therapies are multifaceted. The blessing of cell culture expansion also comes with a burden. During in vitro expansion, stem cells experience a long replicative history and therefore, become subjected to damage from intracellular and extracellular influences. As previously shown cells that are manipulated to obtain an expanded replicative potential are prone to spontaneous transformation in culture. These manipulations help bypass the naturally built-in controls of the cell that govern the delicate balance between cell proliferation, senescence and carcinogenesis. Because of this, there is a risk for patients receiving stem cells that are in vitro expanded. Whether these cells are genetically engineered or harbouring xenogenic compounds, they cannot truly be considered “safe” unless the cells are closely monitored. In the present communication, we will focus on the therapeutic potential of the human mesenchymal stem cells (hMSC) with special focus on their use in cancer therapy. We will consider different mechanisms, by which stem cells can maintain telomeres and thereby the cell’s ability to be expanded in vitro, and also focus on a new therapeutic
Mesenchymal stem cells: a new trend for cell therapy
Acta Pharmacologica Sinica, 2013
Mesenchymal stem cells (MSCs), the major stem cells for cell therapy, have been used in the clinic for approximately 10 years. From animal models to clinical trials, MSCs have afforded promise in the treatment of numerous diseases, mainly tissue injury and immune disorders. In this review, we summarize the recent opinions on methods, timing and cell sources for MSC administration in clinical applications, and provide an overview of mechanisms that are significant in MSC-mediated therapies. Although MSCs for cell therapy have been shown to be safe and effective, there are still challenges that need to be tackled before their wide application in the clinic.
Therapeutic Potential of Mesenchymal Stem Cells for Cancer Therapy
Frontiers in Bioengineering and Biotechnology, 2020
Mesenchymal stem cells (MSCs) are among the most frequently used cell type for regenerative medicine. A large number of studies have shown the beneficial effects of MSC-based therapies to treat different pathologies, including neurological disorders, cardiac ischemia, diabetes, and bone and cartilage diseases. However, the therapeutic potential of MSCs in cancer is still controversial. While some studies indicate that MSCs may contribute to cancer pathogenesis, emerging data reported the suppressive effects of MSCs on cancer cells. Because of this reality, a sustained effort to understand when MSCs promote or suppress tumor development is needed before planning a MSCbased therapy for cancer. Herein, we provide an overview on the therapeutic application of MSCs for regenerative medicine and the processes that orchestrates tissue repair, with a special emphasis placed on cancer, including central nervous system tumors. Furthermore, we will discuss the current evidence regarding the double-edged sword of MSCs in oncological treatment and the latest advances in MSC-based anti-cancer agent delivery systems.