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Cellular and Molecular Life Sciences :... Nov 2019Uncontrolled scarring, or fibrosis, can interfere with the normal function of virtually all tissues of the body, ultimately leading to organ failure and death. Fibrotic... (Review)
Review
Uncontrolled scarring, or fibrosis, can interfere with the normal function of virtually all tissues of the body, ultimately leading to organ failure and death. Fibrotic diseases represent a major cause of death in industrialized countries. Unfortunately, no curative treatments for these conditions are yet available, highlighting the critical need for a better fundamental understanding of molecular mechanisms that may be therapeutically tractable. The ultimate indispensable effector cells responsible for deposition of extracellular matrix proteins that comprise scars are mesenchymal cells, namely fibroblasts and myofibroblasts. In this review, we focus on the biology of these cells and the molecular mechanisms that regulate their pertinent functions. We discuss key pro-fibrotic mediators, signaling pathways, and transcription factors that dictate their activation and persistence. Because of their possible clinical and therapeutic relevance, we also consider potential brakes on mesenchymal cell activation and cellular processes that may facilitate myofibroblast clearance from fibrotic tissue-topics that have in general been understudied.
Topics: Cell Differentiation; Extracellular Matrix; Fibroblasts; Fibrosis; Humans; Mesenchymal Stem Cells; Myofibroblasts; RNA, Untranslated; Signal Transduction
PubMed: 31563998
DOI: 10.1007/s00018-019-03212-3 -
Stem Cells and Development Jan 2020Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) are the primary effective source in stem cell-dependent regenerative medicine due to their... (Review)
Review
Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) are the primary effective source in stem cell-dependent regenerative medicine due to their preponderances over direct MSC implantation. An increasing number of studies have been carried out on MSC-sEV derived from different types of cells, and their function of accelerating tissue repair was proved. However, only a few researches were able to demonstrate the functional cargoes in MSC-sEV or their mechanisms in promoting tissue recovery. In this review, we present current achievements in discovering MSC-sEV-carried RNAs and proteins as promoters in tissue regeneration. Their therapeutic function includes modulating immune reactivity, promoting angiogenesis, and accelerating cell proliferation and migration through orchestrates of cell signaling pathways.
Topics: Animals; Cell Movement; Cell Proliferation; Extracellular Vesicles; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Regeneration; Regenerative Medicine; Signal Transduction
PubMed: 31691632
DOI: 10.1089/scd.2019.0131 -
Cellular and Molecular Life Sciences :... Jul 2017In addition to being multi-potent, mesenchymal stem cells (MSCs) possess immunomodulatory functions that have been investigated as potential treatments in various immune... (Review)
Review
In addition to being multi-potent, mesenchymal stem cells (MSCs) possess immunomodulatory functions that have been investigated as potential treatments in various immune disorders. MSCs can robustly interact with cells of the innate and adaptive immune systems, either through direct cell-cell contact or through their secretome. In this review, we discuss current findings regarding the interplay between MSCs and different immune cell subsets. We also draw attention to the mechanisms involved.
Topics: Animals; Humans; Immune System; Immunomodulation; Mesenchymal Stem Cells; Models, Biological
PubMed: 28214990
DOI: 10.1007/s00018-017-2473-5 -
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 -
Journal of Cellular Physiology Nov 2016Changes in epigenetic marks are known to be important regulatory factors in stem cell fate determination and differentiation. In the past years, the investigation of the... (Review)
Review
Changes in epigenetic marks are known to be important regulatory factors in stem cell fate determination and differentiation. In the past years, the investigation of the epigenetic regulation of stem cell biology has largely focused on embryonic stem cells (ESCs). Contrarily, less is known about the epigenetic control of gene expression during differentiation of adult stem cells (AdSCs). Among AdSCs, mesenchymal stem cells (MSCs) are the most investigated stem cell population because of their enormous potential for therapeutic applications in regenerative medicine and tissue engineering. In this review, we analyze the main studies addressing the epigenetic changes in MSC landscape during in vitro cultivation and replicative senescence, as well as follow osteocyte, chondrocyte, and adipocyte differentiation. In these studies, histone acetylation, DNA methylation, and miRNA expression are among the most investigated phenomena. We describe also epigenetic changes that are associated with in vitro MSC trans-differentiation. Although at the at initial stage, the epigenetics of MSCs promise to have profound implications for stem cell basic and applied research. J. Cell. Physiol. 231: 2393-2401, 2016. © 2016 Wiley Periodicals, Inc.
Topics: Cell Differentiation; Epigenesis, Genetic; Humans; Mesenchymal Stem Cells; Models, Biological
PubMed: 26960183
DOI: 10.1002/jcp.25371 -
Biochemical and Biophysical Research... Sep 2018Translin, a highly conserved DNA/RNA binding protein that forms a hetero-octamer together with Translin-associated factor X (TRAX), possesses a broad variety of...
Translin, a highly conserved DNA/RNA binding protein that forms a hetero-octamer together with Translin-associated factor X (TRAX), possesses a broad variety of functions, including RNA processing and DNA repair. Recent studies have reported that Translin is involved in mesenchymal cell physiology. Thus, here we analyzed the intrinsic role of Translin in mesenchymal cell proliferation and differentiation. Translin-deficient E11.5 mouse embryonic fibroblasts showed enhanced growth. Translin-deficient bone marrow-derived mesenchymal stem cells showed substantial expansion in vivo and enhanced proliferation in vitro. These cells also showed enhanced osteogenic and adipocytic differentiation. Histological analyses showed adipocytic hypertrophy in various adipose tissues. Translin knockout did not affect the growth of subcutaneous white adipose tissue-derived stem cells, but enhanced adipocytic differentiation was observed in vitro. Contrary to previous reports, in vitro-fertilized Translin-null mice were not runted and exhibited normal metabolic homeostasis, indicating the fragility of these mice to environmental conditions. Together, these data suggest that Translin plays an intrinsic role in restricting mesenchymal cell proliferation and differentiation.
Topics: Adipose Tissue; Animals; Bone Marrow Cells; Cell Differentiation; Cell Proliferation; DNA-Binding Proteins; Female; Fibroblasts; Male; Mesenchymal Stem Cells; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteogenesis; RNA-Binding Proteins
PubMed: 30172368
DOI: 10.1016/j.bbrc.2018.08.141 -
Journal of Cell Science Nov 2022Mesenchymal condensation is a prevalent morphogenetic transition that is essential in chondrogenesis. However, the current understanding of condensation mechanisms is...
Mesenchymal condensation is a prevalent morphogenetic transition that is essential in chondrogenesis. However, the current understanding of condensation mechanisms is limited. In vivo, progenitor cells directionally migrate from the surrounding loose mesenchyme towards regions of increasing matrix adherence (the condensation centers), which is accompanied by the upregulation of fibronectin. Here, we focused on the mechanisms of cell migration during mesenchymal cell condensation and the effects of matrix adherence. Dendrimer-based nanopatterns of the cell-adhesive peptide arginine-glycine-aspartic acid (RGD), which is present in fibronectin, were used to regulate substrate adhesion. We recorded collective and single-cell migration of mesenchymal stem cells, under chondrogenic induction, using live-cell imaging. Our results show that the cell migration mode of single cells depends on substrate adhesiveness, and that cell directionality controls cell condensation and the fusion of condensates. Inhibition experiments revealed that cell-cell interactions mediated by N-cadherin (also known as CDH2) are also pivotal for directional migration of cell condensates by maintaining cell-cell cohesion, thus suggesting a fine interplay between cell-matrix and cell-cell adhesions. Our results shed light on the role of cell interactions with a fibronectin-depositing matrix during chondrogenesis in vitro, with possible applications in regenerative medicine. This article has an associated First Person interview with the first author of the paper.
Topics: Humans; Chondrogenesis; Fibronectins; Mesenchymal Stem Cells; Mesoderm; Cadherins; Cell Adhesion; Cell Differentiation
PubMed: 36274586
DOI: 10.1242/jcs.260241 -
Current Stem Cell Research & Therapy 2018Autoimmune disease is a refractory disease. Accumulating Evidence has revealed that the manipulation of mesenchymal stem cells may have the potential to control or even... (Review)
Review
BACKGROUND
Autoimmune disease is a refractory disease. Accumulating Evidence has revealed that the manipulation of mesenchymal stem cells may have the potential to control or even treat autoimmune diseases. Human gingiva-derived mesenchymal stem cells (GMSCs) are emerging as a new line of mesenchymal stem cells that have displayed some potential advantages in controlling and treating autoimmune diseases.
OBJECTIVE
In this review, we briefly update the current understanding on the biology of GMSCs and their effects on preventing and treating autoimmune diseases.
CONCLUSION
The availability of gingival mesenchymal stem cells (GMSCs), together with their potent capacity of multi-directional differentiation and inflammatory modulation, making GMSCs an ideal subtype of MSCs in treating autoimmune disease. Our and other studies have launched the earliest appraisal on GMSCs and carried out a lot of biological researches. The clinical trial of GMSCs on patients with autoimmune diseases will further approve their therapeutic effects, as well as its cellular and molecular mechanisms.
Topics: Animals; Autoimmune Diseases; Cell Differentiation; Cell Proliferation; Disease Models, Animal; Gingiva; Humans; Immunomodulation; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 29468980
DOI: 10.2174/1574888X13666180220141114 -
Stem Cells Translational Medicine Sep 2018The development of mesenchymal stem cells (MSCs) as cell-based drug delivery vectors for numerous clinical indications, including cancer, has significant promise.... (Review)
Review
The development of mesenchymal stem cells (MSCs) as cell-based drug delivery vectors for numerous clinical indications, including cancer, has significant promise. However, a considerable challenge for effective translation of these approaches is the limited tumor tropism and broad biodistribution observed using conventional MSCs, which raises concerns for toxicity to nontarget peripheral tissues (i.e., the bad). Consequently, there are a variety of synthetic engineering platforms in active development to improve tumor-selective targeting via increased homing efficiency and/or specificity of drug activation, some of which are already being evaluated clinically (i.e., the good). Unfortunately, the lack of robust quantification and widespread adoption of standardized methodologies with high sensitivity and resolution has made accurate comparisons across studies difficult, which has significantly impeded progress (i.e., the ugly). Herein, we provide a concise review of active and passive MSC homing mechanisms and biodistribution postinfusion; in addition to in vivo cell tracking methodologies and strategies to enhance tumor targeting with a focus on MSC-based drug delivery strategies for cancer therapy. Stem Cells Translational Medicine 2018;1-13.
Topics: Animals; Antineoplastic Agents; Drug Carriers; Humans; Immunomodulation; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Neoplasms; Oncolytic Virotherapy; Prodrugs
PubMed: 30070053
DOI: 10.1002/sctm.18-0024 -
European Journal of Medical Research Jul 2016The stem cell as the building block necessary for tissue reparation and homeostasis plays a major role in regenerative medicine. Their unique property of being... (Review)
Review
The stem cell as the building block necessary for tissue reparation and homeostasis plays a major role in regenerative medicine. Their unique property of being pluripotent, able to control immune process and even secrete a whole army of anabolic mediators, draws interest. While new arthroscopic procedures and techniques involving stem cells have been established over the last decade with improved outcomes, failures and dissatisfaction still occur. Therefore, there is increasing interest in ways to improve the healing response. MSCs are particularly promising for this task given their regenerative potential. While methods of isolating those cells are no longer poses a challenge, the best way of application is not clear. Several experiments in the realm of basic science and animal models have recently been published, addressing this issue, yet the application in clinical practice has lagged. This review provides an overview addressing the current standing of MSCs in the field of arthroscopic surgery.
Topics: Animals; Arthroscopy; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 27411303
DOI: 10.1186/s40001-016-0224-y