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Chemistry and Physics of Lipids Oct 2017Oxysterols are oxidized products of cholesterol that play several roles in various pathophysiological processes, including the control of lipid metabolism, immunological... (Review)
Review
Oxysterols are oxidized products of cholesterol that play several roles in various pathophysiological processes, including the control of lipid metabolism, immunological processes, and cytotoxicity. Mesenchymal stem cells are multipotent cells with properties of self-renewal and the ability to differentiate into other cell types, including osteoblasts and adipocytes. Here, we review the literature regarding the effects of oxysterols on mesenchymal stem cell differentiation and the main signaling pathways involved in this process.
Topics: Animals; Cell Differentiation; Humans; Mesenchymal Stem Cells; Oxysterols
PubMed: 28669640
DOI: 10.1016/j.chemphyslip.2017.06.009 -
Seminars in Cell & Developmental Biology Apr 2015MSCs are an extensively used cell type in clinical trials today. The initial rationale for their clinical testing was based on their differentiation potential. However,... (Review)
Review
MSCs are an extensively used cell type in clinical trials today. The initial rationale for their clinical testing was based on their differentiation potential. However, the lack of correlation between functional improvement and cell engraftment or differentiation at the site of injury has led to the proposal that MSCs exert their effects not through their differentiation potential but through their secreted product, more specifically, exosomes, a type of extracellular vesicle. We propose here that MSC exosomes function as an extension of MSC's biological role as tissue stromal support cells. Like their cell source, MSC exosomes help maintain tissue homeostasis for optimal tissue function. They target housekeeping biological processes that operate ubiquitously in all tissues and are critical in maintaining tissue homeostasis, enabling cells to recover critical cellular functions and begin repair and regeneration. This hypothesis provides a rationale for the therapeutic efficacy of MSCs and their secreted exosomes in a wide spectrum of diseases. Here, we give a brief introduction of the biogenesis of MSC exosomes, review their physiological functions and highlight some of their biochemical potential to illustrate how MSC exosomes could restore tissue homeostasis leading to tissue recovery and repair.
Topics: Animals; Exosomes; Humans; Immunomodulation; Mesenchymal Stem Cells; Proteome
PubMed: 25765629
DOI: 10.1016/j.semcdb.2015.03.001 -
Dermatologic Therapy Nov 2022Exosomes are nano-sized extracellular vesicles released by the majority of the cell types. Exosomes play a major role in intercellular communication via transferring... (Review)
Review
Exosomes are nano-sized extracellular vesicles released by the majority of the cell types. Exosomes play a major role in intercellular communication via transferring cargoes between cells and altering specific functions of the target cells. The interest in the biological activities of exosomes has been increasing and their therapeutic role has already been demonstrated in various diseases. Recently, there is growing evidence that stem cell-derived exosomes (including mesenchymal stem cell, umbilical cord-derived mesenchymal cell, adipose-derived stem cell, and pluripotent stem cell) can also be used in a variety of skin conditions due to their regenerative and anti-inflammatory capacity. In this paper, we will provide a brief overview of recent studies on practical applications of exosomes in several dermatologic conditions and their potential mechanisms. By elucidating the different mechanisms and therapeutic roles of exosomes in various disease conditions, we hope dermatologists and other clinicians to establish better strategies for disease treatment with further research.
Topics: Humans; Exosomes; Mesenchymal Stem Cells; Adipose Tissue
PubMed: 36183094
DOI: 10.1111/dth.15883 -
Cell Communication and Signaling : CCS Sep 2016Tumor development and tumor progression is not only determined by the corresponding tumor cells but also by the tumor microenvironment. This includes an orchestrated... (Review)
Review
Tumor development and tumor progression is not only determined by the corresponding tumor cells but also by the tumor microenvironment. This includes an orchestrated network of interacting cell types (e.g. immune cells, endothelial cells, fibroblasts, and mesenchymal stroma/stem cells (MSC)) via the extracellular matrix and soluble factors such as cytokines, chemokines, growth factors and various metabolites. Cell populations of the tumor microenvironment can interact directly and indirectly with cancer cells by mutually altering properties and functions of the involved partners. Particularly, mesenchymal stroma/stem cells (MSC) play an important role during carcinogenesis exhibiting different types of intercellular communication. Accordingly, this work focusses on diverse mechanisms of interaction between MSC and cancer cells. Moreover, some functional changes and consequences for both cell types are summarized which can eventually result in the establishment of a carcinoma stem cell niche (CSCN) or the generation of new tumor cell populations by MSC-tumor cell fusion.
Topics: Animals; Cell Communication; Extracellular Vesicles; Humans; Mesenchymal Stem Cells; Signal Transduction; Tumor Microenvironment
PubMed: 27608835
DOI: 10.1186/s12964-016-0143-0 -
Journal of Hepatology Jun 2018The therapeutic potential of mesenchymal stromal cells (MSCs) in the treatment of liver fibrosis is predominantly based on their immunosuppressive properties, and their... (Review)
Review
The therapeutic potential of mesenchymal stromal cells (MSCs) in the treatment of liver fibrosis is predominantly based on their immunosuppressive properties, and their ability to secrete various trophic factors. This potential has been investigated in clinical and preclinical studies. Although the therapeutic mechanisms of MSC transplantation are still not fully characterised, accumulating evidence has revealed that various trophic factors secreted by MSCs play key therapeutic roles in regeneration by alleviating inflammation, apoptosis, and fibrosis as well as stimulating angiogenesis and tissue regeneration in damaged liver. In this review, we summarise the safety, efficacy, potential transplantation routes and therapeutic effects of MSCs in patients with liver fibrosis. We also discuss some of the key strategies to enhance the functionality of MSCs, which include sorting and/or priming with factors such as cytokines, as well as genetic engineering.
Topics: Animals; Cell Differentiation; Clinical Trials as Topic; Gene Editing; Humans; Liver Diseases; Liver Regeneration; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 29425678
DOI: 10.1016/j.jhep.2018.01.030 -
Cell Stem Cell Mar 2015Mesenchymal stromal cells (MSCs) are heterogeneous and primitive cells discovered first in the bone marrow (BM). They have putative roles in maintaining tissue... (Review)
Review
Mesenchymal stromal cells (MSCs) are heterogeneous and primitive cells discovered first in the bone marrow (BM). They have putative roles in maintaining tissue homeostasis and are increasingly recognized as components of stem cell niches, which are best defined in the blood. The absence of in vivo MSC markers has limited our ability to track their behavior in vivo and draw comparisons with in vitro observations. Here we review the historical background of BM-MSCs, advances made in their prospective isolation, their developmental origin and contribution to maintaining subsets of hematopoietic cells, and how mesenchymal cells contribute to other stem cell niches.
Topics: Animals; Antigens, Differentiation; Bone Marrow Cells; Humans; Mesenchymal Stem Cells; Stem Cell Niche
PubMed: 25748931
DOI: 10.1016/j.stem.2015.02.019 -
Advances in Experimental Medicine and... 2021Adipose stem cells (ASCs) have gained attention in the fields of stem cells regenerative medicine due to their multifaceted therapeutic capabilities. Promising... (Review)
Review
Adipose stem cells (ASCs) have gained attention in the fields of stem cells regenerative medicine due to their multifaceted therapeutic capabilities. Promising preclinical evidence of ASCs has supported the substantial interest in the use of these cells as therapy for human disease. ASCs are an adult stem cell resident in adipose tissue with the potential to differentiation along mesenchymal lineages. They also are known to be recruited to sites of inflammation where they exhibit strong immunomodulatory capabilities to promote wound healing and regeneration. ASCs can be isolated from adipose tissue at a relatively high yield compared to their mesenchymal cell counterparts: bone marrow-derived mesenchymal stem cells (BM-MSCs). Like BM-MSCs, ASCs are easily culture expanded and have a reduced immunogenicity or are perhaps immune privileged, making them attractive options for cellular therapy. Additionally, the heterogeneous cellular product obtained after digestion of adipose tissue, called the stromal vascular fraction (SVF), contains ASCs and several populations of stromal and immune cells. Both the SVF and culture expanded ASCs have the potential to be therapeutic in various diseases. This review will focus on the preclinical and clinical evidence of SVF and ASCs, which make them potential candidates for therapy in regenerative medicine and inflammatory disease processes.
Topics: Adipocytes; Adipose Tissue; Cell Differentiation; Humans; Mesenchymal Stem Cells; Stem Cells
PubMed: 30051318
DOI: 10.1007/5584_2018_248 -
Cell Metabolism Mar 2017Intermittent PTH administration builds bone mass and prevents fractures, but its mechanism of action is unclear. We genetically deleted the PTH/PTHrP receptor (PTH1R)...
Intermittent PTH administration builds bone mass and prevents fractures, but its mechanism of action is unclear. We genetically deleted the PTH/PTHrP receptor (PTH1R) in mesenchymal stem cells using Prx1Cre and found low bone formation, increased bone resorption, and high bone marrow adipose tissue (BMAT). Bone marrow adipocytes traced to Prx1 and expressed classic adipogenic markers and high receptor activator of nuclear factor kappa B ligand (Rankl) expression. RANKL levels were also elevated in bone marrow supernatant and serum, but undetectable in other adipose depots. By cell sorting, Pref1RANKL marrow progenitors were twice as great in mutant versus control marrow. Intermittent PTH administration to control mice reduced BMAT significantly. A similar finding was noted in male osteoporotic patients. Thus, marrow adipocytes exhibit osteogenic and adipogenic characteristics, are uniquely responsive to PTH, and secrete RANKL. These studies reveal an important mechanism for PTH's therapeutic action through its ability to direct mesenchymal cell fate.
Topics: Adipocytes; Adipogenesis; Adipose Tissue; Animals; Biomarkers; Bone Marrow Cells; Bone and Bones; Cell Count; Cell Lineage; Humans; Integrases; Male; Mesenchymal Stem Cells; Mice; Osteoblasts; Osteoporosis; Parathyroid Hormone; Phenotype; RANK Ligand; Receptor, Parathyroid Hormone, Type 1; Signal Transduction; Skull
PubMed: 28162969
DOI: 10.1016/j.cmet.2017.01.001 -
European Journal of Medical Genetics Feb 2018Epigenetic factors are known to play a major role in determining stem cell fate and differentiation. Mesenchymal stem cells are the most studied population of stem cells... (Review)
Review
Epigenetic factors are known to play a major role in determining stem cell fate and differentiation. Mesenchymal stem cells are the most studied population of stem cells due to their important applications in experimental biology and regenerative medicine. After a brief overview on mesenchymal stem cells, this review aims to highlight the role of epigenetic changes on mesenchymal stem cells biology and differentiation protocols with a focus on osteocytic, chondrocytic and adipocytic differentiation. Chromatin remodeling, DNA methylation, histone modifications and miRNA expression will be investigated. The impact of epigenetics on transdifferentiation of mesenchymal stem cells will also be discussed. Indeed, epigenetic modulation appears to constitute a promising experimental target in stem cell basic and translational research.
Topics: Animals; Cell Differentiation; Chromatin Assembly and Disassembly; DNA Methylation; Epigenesis, Genetic; Histone Code; Humans; Mesenchymal Stem Cells
PubMed: 29079547
DOI: 10.1016/j.ejmg.2017.10.015 -
Seminars in Cell & Developmental Biology Nov 2019As treatments for diseases throughout the body progress, treatment for many brain diseases has been at a standstill due to difficulties in drug delivery. While new drugs... (Review)
Review
As treatments for diseases throughout the body progress, treatment for many brain diseases has been at a standstill due to difficulties in drug delivery. While new drugs are being discovered in vitro, these therapies are often hindered by inefficient tissue distribution and, more commonly, an inability to cross the blood brain barrier. Mesenchymal stem cells are thus being investigated as a delivery tool to directly target therapies to the brain to treat wide array of brain diseases. This review discusses the use of mesenchymal stem cells in hypoxic disease (hypoxic ischemic encephalopathy), an inflammatory neurodegenerative disease (multiple sclerosis), and a malignant condition (glioma).
Topics: Animals; Blood-Brain Barrier; Brain Diseases; Cell-Derived Microparticles; Cellular Microenvironment; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 30922957
DOI: 10.1016/j.semcdb.2019.03.003