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European Journal of Cell Biology Jan 2017Mesenchymal stem cells (MSCs) have extensive potentials, which make them attractive candidates for the developmental biology, drug discovery and regenerative medicine.... (Review)
Review
Mesenchymal stem cells (MSCs) have extensive potentials, which make them attractive candidates for the developmental biology, drug discovery and regenerative medicine. However, the use of MSCs is limited by their scarceness in tissues and in culture conditions. They also exhibit various degrees of potency which subsequently influencing their applications. Nowadays, questions remain about how self-renewal and differentiation of MSCs can be controlled in vitro and in vivo, how they will behave and migrate to the right place and how they modulate the immune system. Therefore, identification of factors and culture conditions to affect the fate and function of MSCs may be effective to enhance their applications in clinical situations. Studies have indicated that the fate of MSCs in culture is influenced by various external factors, including the specific cell source, donor age, plating density, passage number and plastic surface quality. Some other factors such as cell culture media and their supplementary factors, O concentration, mechano-/electro-stimuli and three-dimensional scaffolds are also shown to be influential. This review addresses the current state of MSC research for describing and discussing the findings about external factors that influence the fate and function of MSCs. Additionally, the new discoveries and suggestions regarding their molecular mechanisms will be explained.
Topics: Animals; Cell Culture Techniques; Humans; Mesenchymal Stem Cells
PubMed: 27988106
DOI: 10.1016/j.ejcb.2016.11.003 -
American Journal of Physiology.... May 2011An exquisite equilibrium between cell proliferation and programmed cell death is required to maintain physiological homeostasis. In inflammatory bowel disease, and... (Review)
Review
An exquisite equilibrium between cell proliferation and programmed cell death is required to maintain physiological homeostasis. In inflammatory bowel disease, and especially in Crohn's disease, enhanced proliferation along with defective apoptosis of immune cells are considered key elements of pathogenesis. Despite the relatively limited attention that has been given to research efforts devoted to intestinal fibrosis to date, there is evidence suggesting that enhanced proliferation along with defective programmed cell death of mesenchymal cells can significantly contribute to the development of excessive fibrogenesis in many different tissues. Moreover, some therapies have demonstrated potential antifibrogenic efficacy through the regulation of mesenchymal cell proliferation and programmed cell death. Further understanding of the pathways involved in the regulation of mesenchymal cell proliferation and apoptosis is, however, required.
Topics: Animals; Apoptosis; Cell Proliferation; Crohn Disease; Fibrosis; Humans; Inflammatory Bowel Diseases; Mesenchymal Stem Cells
PubMed: 21233275
DOI: 10.1152/ajpgi.00504.2010 -
Current Opinion in Rheumatology Jan 2013Cells of mesenchymal origin are strongly influenced by their biomechanical environment. They also help to shape tissue architecture and reciprocally influence tissue... (Review)
Review
PURPOSE OF REVIEW
Cells of mesenchymal origin are strongly influenced by their biomechanical environment. They also help to shape tissue architecture and reciprocally influence tissue mechanical environments through their capacity to deposit, remodel, and resorb extracellular matrix and to promote tissue vascularization. Although mechanical regulation of cell function and tissue remodeling has long been appreciated in other contexts, the purpose of this review is to highlight the increasing appreciation of its importance in fibrosis and hypertrophic scarring.
RECENT FINDINGS
Experiments in both animal and cellular model systems have demonstrated pivotal roles for the biomechanical environment in regulating myofibroblast differentiation and contraction, endothelial barrier function and angiogenesis, and mesenchymal stem cell fate decisions. Through these studies, a better understanding of the molecular mechanisms transducing the biomechanical environment is emerging, with prominent and interacting roles recently identified for key network components including transforming growth factor-β/SMAD, focal adhesion kinase, MRTFs, Wnt/β-catenin and YAP/TAZ signaling pathways.
SUMMARY
Progress in understanding biomechanical regulation of mesenchymal cell function is leading to novel approaches for improving clinical outcomes in fibrotic diseases and wound healing. These approaches include interventions aimed at modifying the tissue biomechanical environment, and efforts to target mesenchymal cell activation by, and reciprocal interactions with, the mechanical environment.
Topics: Animals; Cicatrix, Hypertrophic; Extracellular Matrix; Fibrosis; Humans; Mechanotransduction, Cellular; Mesenchymal Stem Cells; Myofibroblasts; Wound Healing
PubMed: 23114589
DOI: 10.1097/BOR.0b013e32835b13cd -
Tissue Engineering 2005Adult stem cells provide replacement and repair descendants for normal turnover or injured tissues. These cells have been isolated and expanded in culture, and their use... (Review)
Review
Adult stem cells provide replacement and repair descendants for normal turnover or injured tissues. These cells have been isolated and expanded in culture, and their use for therapeutic strategies requires technologies not yet perfected. In the 1970s, the embryonic chick limb bud mesenchymal cell culture system provided data on the differentiation of cartilage, bone, and muscle. In the 1980s, we used this limb bud cell system as an assay for the purification of inductive factors in bone. In the 1990s, we used the expertise gained with embryonic mesenchymal progenitor cells in culture to develop the technology for isolating, expanding, and preserving the stem cell capacity of adult bone marrow-derived mesenchymal stem cells (MSCs). The 1990s brought us into the new field of tissue engineering, where we used MSCs with site-specific delivery vehicles to repair cartilage, bone, tendon, marrow stroma, muscle, and other connective tissues. In the beginning of the 21st century, we have made substantial advances: the most important is the development of a cell-coating technology, called painting, that allows us to introduce informational proteins to the outer surface of cells. These paints can serve as targeting addresses to specifically dock MSCs or other reparative cells to unique tissue addresses. The scientific and clinical challenge remains: to perfect cell-based tissue-engineering protocols to utilize the body's own rejuvenation capabilities by managing surgical implantations of scaffolds, bioactive factors, and reparative cells to regenerate damaged or diseased skeletal tissues.
Topics: Bioprosthesis; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Orthopedic Procedures; Prosthesis Design; Plastic Surgery Procedures; Tissue Engineering
PubMed: 16144456
DOI: 10.1089/ten.2005.11.1198 -
International Journal of Molecular... Aug 2021Mesenchymal stem cells, also called medicinal signaling cells (MSC), have been studied regarding their potential to facilitate tissue repair for >30 years. Such cells,... (Review)
Review
What Molecular Recognition Systems Do Mesenchymal Stem Cells/Medicinal Signaling Cells (MSC) Use to Facilitate Cell-Cell and Cell Matrix Interactions? A Review of Evidence and Options.
Mesenchymal stem cells, also called medicinal signaling cells (MSC), have been studied regarding their potential to facilitate tissue repair for >30 years. Such cells, derived from multiple tissues and species, are capable of differentiation to a number of lineages (chondrocytes, adipocytes, bone cells). However, MSC are believed to be quite heterogeneous with regard to several characteristics, and the large number of studies performed thus far have met with limited or restricted success. Thus, there is more to understand about these cells, including the molecular recognition systems that are used by these cells to perform their functions, to enhance the realization of their potential to effect tissue repair. This perspective article reviews what is known regarding the recognition systems available to MSC, the possible systems that could be looked for, and alternatives to enhance their localization to specific injury sites and increase their subsequent facilitation of tissue repair. MSC are reported to express recognition molecules of the integrin family. However, there are a number of other recognition molecules that also could be involved such as lectins, inducible lectins, or even a MSC-specific family of molecules unique to these cells. Finally, it may be possible to engineer expression of recognition molecules on the surface of MSC to enhance their function in vivo artificially. Thus, improved understanding of recognition molecules on MSC could further their success in fostering tissue repair.
Topics: Animals; Cell Communication; Extracellular Matrix; Humans; Mesenchymal Stem Cells; Signal Transduction; Wound Healing
PubMed: 34445341
DOI: 10.3390/ijms22168637 -
Current Opinion in Lipidology Dec 2007Mesenchymal stem cells (or multipotent stromal cells) are emerging as a potent cell type for cardiac cell therapy. This review describes the potential of cardiac... (Review)
Review
PURPOSE OF REVIEW
Mesenchymal stem cells (or multipotent stromal cells) are emerging as a potent cell type for cardiac cell therapy. This review describes the potential of cardiac mesenchymal stem cell therapy, but also highlights some recently discovered less favorable mesenchymal stem cell characteristics.
RECENT FINDINGS
Mesenchymal stem cells exert a beneficial effect on cardiac function upon administration to the ischemic myocardium. The mode of action does not seem to involve differentiation into cardiomyocytes and vascular cells. A robust effect on revascularization and remodeling is observed, however, most likely mediated by paracrine factors. Recently identified drawbacks associated with cardiac mesenchymal stem cell therapy include differentiation into unwanted mesenchymal cell types such as osteocytes and adipocytes, the occurrence of cytogenetic instability upon prolonged expansion, and immunization when used in an allogeneic setting.
SUMMARY
The application of mesenchymal stem cells is a novel strategy with therapeutic potential for cardiac repair. Strategies are needed, however, to optimize their therapeutic potential while minimizing their potential clinical risks.
Topics: Animals; Cell Differentiation; Cell Transformation, Neoplastic; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Myocardial Ischemia
PubMed: 17993810
DOI: 10.1097/MOL.0b013e3282f0dd1f -
Stem Cell Reviews and Reports Apr 2018Mesenchymal stem cells (MSCs) are promising resource for the therapy of inflammatory bowel diseases (IBDs) on the grounds of their differentiation capabilities and... (Review)
Review
Mesenchymal stem cells (MSCs) are promising resource for the therapy of inflammatory bowel diseases (IBDs) on the grounds of their differentiation capabilities and immuno-modulatory characteristics. Results of clinical studies indicate that local application of MSCs is a secure and beneficial approach for the treatment of perianal fistulas while systemic application of MSCs leads to the attenuation or aggravation of IBDs. Herein, we emphasized molecular mechanisms and approaches that should improve efficacy of MSC-based therapy of IBDs.
Topics: Animals; Cell- and Tissue-Based Therapy; Humans; Inflammatory Bowel Diseases; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 29177796
DOI: 10.1007/s12015-017-9789-2 -
Vitamins and Hormones 2011Mesenchymal stem cells (MSCs) have the ability to self-renew and differentiate into multiple lineages making them an appropriate candidate for stem cell therapy. In... (Review)
Review
Mesenchymal stem cells (MSCs) have the ability to self-renew and differentiate into multiple lineages making them an appropriate candidate for stem cell therapy. In spite of achieving considerable success in preclinical models, limited success has been achieved in clinical settings with MSCs. A major impediment that is faced is low survival of MSCs in injured tissues following implantation. In order to enhance the reparative properties of MSCs, it is vital to understand the molecular signals that regulate MSC survival and self-renewal. This review assimilates information that characterizes MSCs and mentions their utilization in myocardial infarction therapy. Additionally, our attempt herein is to gather pertinent published information regarding the role of canonical Wnt and BMP signaling in regulating the potential of MSCs to self-renew, proliferate, differentiate, and survive.
Topics: Animals; Cell Differentiation; Humans; Immunomodulation; Mesenchymal Stem Cells; Stem Cell Niche
PubMed: 22127236
DOI: 10.1016/B978-0-12-386015-6.00023-8 -
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 -
Biotechnology Progress 2015Human mesenchymal or stromal cells (hMSCs) isolated from various adult tissues are primary candidates in cell therapy and tissue regeneration. Despite promising results... (Review)
Review
Human mesenchymal or stromal cells (hMSCs) isolated from various adult tissues are primary candidates in cell therapy and tissue regeneration. Despite promising results in preclinical studies, robust therapeutic responses to MSC treatment have not been reproducibly demonstrated in clinical trials. In the translation of MSC-based therapy to clinical application, studies of MSC metabolism have significant implication in optimizing bioprocessing conditions to obtain therapeutically competent hMSC population for clinical application. In addition, understanding the contribution of metabolic cues in directing hMSC fate also provides avenues to potentiate their therapeutic effects by modulating their metabolic properties. This review focuses on MSC metabolism and discusses their unique metabolic features in the context of common metabolic properties shared by stem cells. Recent advances in the fundamental understanding of MSC metabolic characteristics in relation to their in vivo origin and metabolic regulation during proliferation, lineage-specific differentiation, and exposure to in vivo ischemic conditions are summarized. Metabolic strategies in directing MSC fate to enhance their therapeutic potential in tissue engineering and regenerative medicine are discussed.
Topics: Animals; Apoptosis; Cell Differentiation; Cell Engineering; Cell Proliferation; Energy Metabolism; Glycolysis; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Rats; Stem Cell Niche; Stem Cell Research
PubMed: 25504836
DOI: 10.1002/btpr.2034