The life and fate of mesenchymal stem cells (original) (raw)
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Tracking inflammation-induced mobilization of mesenchymal stem cells
2012
The act of migration is similar for many cell types. The migratory mechanism of mesenchymal stem cells (MSC) is not completely elucidated, yet many of the initial studies have been based on current understanding of the leukocyte migration. A normal function of MSC is the ability of the cell to migrate to and repair wounded tissue. This wound healing property of MSC originates with migration towards in fl ammatory signals produced by the wounded environment [1]. A tumor and its microenvironment are capable of eliciting a similar in fl ammatory response from the MSC, thus resulting in migration of the MSC towards the tumor microenvironment. We have shown MSC migration both in vitro and in vivo. In this chapter, we elucidate several in vivo methods to study MSC migration and mobilization to the tumor microenvironment. The fi rst model is an exogenous model of MSC migration that can be performed in both xenograft and syngenic systems with in vitro expanded MSC. The second model utilizes transgenic-fl uorescentcolored mice to follow endogenous bone marrow components including MSC. The third technique enables us to analyze data from the transgenic model through multispectral imaging. Furthermore, the migratory phenotype of MSC can be exploited for use in tumor-targeted gene delivery therapy has been ef fi cacious in animal model studies and is an anticipated therapeutic device in clinical trials.
Mesenchymal stem cells: a perspective from in vitro cultures to in vivo migration and niches
European Cells and Materials, 2010
Mesenchymal Stromal Progenitor/Stem Cells (MSCs) are a rare population of non-hematopoietic stromal cells, present in the bone marrow and most connective tissues of the body. They are capable of differentiation into mesenchymal tissues such as bone, cartilage, adipose tissue and muscle. In the absence of specific markers, MSCs have been defined following isolation and culture expansion, by their expression of various molecules including CD90, CD105 and CD73 and absence of markers like CD34, CD45, and CD14. MSCs have extensive proliferative ability in culture in an uncommitted state while retaining their multilineage differentiation potential, which make them attractive candidates for biological cell-based tissue repair approaches. However, their identity in their tissues of origin is not clear and the niches in which they reside are not defined. This review addresses the current state of MSC research including the differentiation potency of culture expanded MSCs, expression of chemokines and their receptors in MSCs-both relevant issues for the advocated use of MSCs for tissue repair and their systemic delivery to the affected tissues. It also reviews current knowledge of MSC niches in their native tissues, addressing the relationship with pericytes. Finally, it provides a scientific basis for the requirement of a thorough characterisation of the endogenous MSC niches within their native tissues in vivo. The knowledge of MSC niches will instruct development of innovative therapeutic measures such as producing pharmacological substances that target endogenous MSCs and their niches in order to activate and guide intrinsic repair and to improve disease outcomes.
Inflammation and the Migration of Mesenchymal Stem Cell
2015
Mesenchymal stem cells are adult non-hematopoietic stem cells with multilineage proliferation and differentiation capabilities. This type of stem cell has the multipotent ability to differentiate into osteocytes, tenocytes, adipocytes, chondrocytes and bone marrow stromal cells. The migration mechanism of mesenchymal stem cell is not yet fully understood, but based on studies that have been done recently by the researchers worldwide shown that the inflammatory process plays an important role for mesenchymal stem cell migration. A number of chemokine that plays a role in the migration of mesenchymal stem cells such as MCP-1 (CCL2), CXCL8, RANTES (CCL5), LL-37, integrin β1, CD44 receptor, CCR2, CCR3, and tyrosine kinase receptors for the following growth factors: IGF -1, PDGF-bb, HGF and VEGF
Acta Biochimica Polonica
The MSCs are immature cells that can be found in numerous different tissue types. In recent years, they have gained considerable attention, particularly with regard to their regenerative properties. Due to their paracrine activity, ability to migrate, adhesion and homing, MSCs currently appear to be the most relevant for therapeutic use. Numerous bioactive molecules secreted by MSCs exert paracrine effects and modulate many physiological processes, such as angiogenesis, immunomodulation and neuroprotection. Cell-cell communication may be also mediated by extracellular vesicles released from the cells. Due to these properties, MSCs have been widely studied for evaluation of their therapeutic benefits expected in the clinical applications. For effective tissue regeneration, transplanted MSCs have to exit the circulation and locate at the site of damage, which is possible because of their ability to migrate, adhere and engraft at the target site. Accumulating evidence suggests that MSC...
Anti-inflammatory effects of mesenchymal stem cells: novel concept for future therapies
Expert Opinion on Biological Therapy, 2008
Background : Mesenchymal stem cells (MSC) are multipotent cells that can be isolated from the bone marrow and expanded in culture relatively easily. Culture-expanded MSC have been used in clinical settings to enhance hematopoietic stem cell engraftment in bone marrow transplant patients and in tissue regeneration therapy. More recently, the anti-inflammatory effects of MSC have generated a great deal of interest. Objective/methods : In this review we describe in vitro assays that have demonstrated how MSC regulate immune cell proliferation, differentiation and phenotype. We also highlight effector molecules produced by MSC that drive this function. In addition, we focus on animal models of lung injury, in which administration of MSC attenuates inflammation, and injury revealing a central role for MSC in mitigating pro-inflammatory networks and amplifying anti-inflammatory signals. Conclusions : The discoveries described herein have contributed to the novel concept of MSC as a therapeutic modality in inflammatory diseases, including acute lung injury.
Activation, homing, and role of the mesenchymal stem cells in the inflammatory environment
Journal of Inflammation Research, 2016
Human mesenchymal stem cells (MSCs) are considered to be a promising source of cells in regenerative medicine. They have large potential to differentiate into various tissuespecific populations and may be isolated from diverse tissues in desired quantities. As cells of potential autologous origin, they allow recipients to avoid the alloantigen responses. They also have the ability to create immunomodulatory microenvironment, and thus help to minimize organ damage caused by the inflammation and cells activated by the immune system. Our knowledge about the reparative, regenerative, and immunomodulatory properties of MSCs is advancing. At present, there is a very comprehensible idea on how MSCs affect the immune system, particularly in relation to the tissue and organ damage on immunological basis. Hitherto a number of effective mechanisms have been described by which MSCs influence the immune responses. These mechanisms include a secretion of soluble bioactive agents, an induction of regulatory T cells, modulation of tolerogenic dendritic cells, as well as induction of anergy and apoptosis. MSCs are thus able to influence both innate and adaptive immune responses. Soluble factors that are released into local microenvironment with their subsequent paracrine effects are keys to the activation. As a result, activated MSCs contribute to the restoration of damaged tissues or organs through various mechanisms facilitating reparative and regenerative processes as well as through immunomodulation itself and differentiation into the cells of the target tissue.
Implications of mesenchymal stem cells in regenerative medicine
Artificial Cells, Nanomedicine, and Biotechnology, 2016
Mesenchymal stem cells (MSCs) are a population of multipotent progenitors which reside in bone marrow, fat, and some other tissues and can be isolated from various adult and fetal tissues. Selfrenewal potential and multipotency are MSC's hallmarks. They have the capacity of proliferation and differentiation into a variety of cell lineages like osteoblasts, condrocytes, adipocytes, fibroblasts, cardiomyocytes. MSCs can be identified by expression of some surface molecules like CD73, CD90, CD105, and lack of hematopoietic specific markers including CD34, CD45, and HLA-DR. They are hopeful tools for regenerative medicine for repairing injured tissues. Many studies have focused on two significant features of MSC therapy: (I) systemically administered MSCs home to sites of ischemia or injury, and (II) MSCs can modulate T-cell-mediated immunological responses. MSCs express chemokine receptors and ligands involved in cells migration and homing process. MSCs induce immunomedulatory effects on the innate (dendritic cells, monocyte, natural killer cells, and neutrophils) and the adaptive immune system cells (T helper-1, cytotoxic T lymphocyte, and B lymphocyte) by secreting soluble factors like TGF-b, IL-10, IDO, PGE-2, sHLA-G5, or by cell-cell interaction. In this review, we discuss the main applications of mesenchymal stem in Regenerative Medicine and known mechanisms of homing and Immunomodulation of MSCs.
Concise Review: Mesenchymal Stem Cells and Translational Medicine: Emerging Issues
Stem Cells Translational Medicine, 2012
Mesenchymal stem cells (MSCs) are emerging as a promising therapeutic approach of cell-based therapy for a wide range of autoimmune disorders and degenerative diseases. In preclinical and clinical studies, MSCs have been shown to be highly efficient in treating graft-versus-host disease, systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, myocardial infarction, liver cirrhosis, inflammatory bowel disease, and other disorders. The underlying therapeutic mechanisms of MSCs include their homing efficiency to the tissue injury sites, their differentiation potential, their capability to produce a large amount of trophic factors, and their immunomodulatory effect. Because tissue damage sites are complicated milieus with distinct types of inflammatory cells and factors, available data have demonstrated that the properties of MSCs could be fundamentally influenced by the inflammatory elements. Thus, an understanding of the interaction between MSCs and the inflammatory microenvironment will provide critical information in revealing the precise in vivo mechanisms of MSC-mediated therapeutic effects and designing more practical protocols for clinical use of these cells.
Journal of Regenerative Medicine & Biology Research, 2020
Mesenchymal Stem Cells (MSCs); which were first described by Alexander Fridenstein in the 1960s; are heterogeneous, non-hematopoietic, adult multipotent stromal progenitor cells that are capable of self-renewal and differentiation into various cell types [1-8]. They can be isolated from various sources including: Bone Marrow (BM) which is the main source, peripheral blood, umbilical cord blood, amniotic fluid, placenta, Adipose Tissue (AT), dental pulp, synovial fluid, salivary glands, liver, lung, skin and skeletal muscles [1-10]. MSCs have the following distinguishing features: adherence to the plastic vessel; capacity to different into osteoblasts, adipocytes and chondrocytes; and being characteristically positive for CD105, CD73, and CD90 and characteristically negative for CD45, CD34, CD11b, CD14, CD19, CD79a, and human leukocyte antigen (HLA)-DR on flow cytometry [1,3,4,11-16]. However, under certain circumstances, MSCs obtained from BM, AT, and other sources may express CD34 surface markers [5-8,17]. Additionally, MSCs do not express significant histocompatibility complexes and immune stimulating molecules. Consequently, they escape immune surveillance and their clinical utilization in transplantation is not associated with graft rejection [10].