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Journal of Tissue Viability Aug 2017Venous leg ulcers (VLU) are a prevalent and reoccurring type of complicated wound, turning as a considerable public healthcare issue, with critical social and economic... (Review)
Review
Venous leg ulcers (VLU) are a prevalent and reoccurring type of complicated wound, turning as a considerable public healthcare issue, with critical social and economic concern. There are both medical and surgical therapies to treat venous leg ulcers; however, a cure does not yet exist. Mesenchymal stem cells (MSC) are capable and proved of accelerating wound healing in vivo and their study with human chronic wounds is currently awaited. MSCs are a promising source of adult progenitor cells for cellular therapy and have been demonstrated to differentiate into various mesenchymal cell lineages. They have a crucial and integral role in native wound healing by regulating immune response and inflammation. Improved understanding of the cellular and molecular mechanisms at work in delayed wound healing compels to the development of cellular therapy in VLU. This review focuses on the current treatment option of VLU and further emphasizing the role of MSCs in accelerating the healing process. With further understanding of the mechanism of action of these cells in wound improvement and, the involvement of cytokines can also be revealed that could be used for the therapeutic purpose for VLU healing. Clinical uses of MSCs have been started already, and induced MSCs are surely a promising tool or compelling therapy for VLU.
Topics: Adult; Humans; Leg; Mesenchymal Stem Cells; Varicose Ulcer; Wound Healing
PubMed: 28619238
DOI: 10.1016/j.jtv.2017.06.001 -
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 Translational Medicine Sep 2020Mesenchymal stem cells (multipotent stromal cells; MSCs) have been under investigation for the treatment of diverse diseases, with many promising outcomes achieved in... (Review)
Review
Mesenchymal stem cells (multipotent stromal cells; MSCs) have been under investigation for the treatment of diverse diseases, with many promising outcomes achieved in animal models and clinical trials. The biological activity of MSC therapies has not been fully resolved which is critical to rationalizing their use and developing strategies to enhance treatment efficacy. Different paradigms have been constructed to explain their mechanism of action, including tissue regeneration, trophic/anti-inflammatory secretion, and immunomodulation. MSCs rarely engraft and differentiate into other cell types after in vivo administration. Furthermore, it is equivocal whether MSCs function via the secretion of many peptide/protein ligands as their therapeutic properties are observed across xenogeneic barriers, which is suggestive of mechanisms involving mediators conserved between species. Oxidative stress is concomitant with cellular injury, inflammation, and dysregulated metabolism which are involved in many pathologies. Growing evidence supports that MSCs exert antioxidant properties in a variety of animal models of disease, which may explain their cytoprotective and anti-inflammatory properties. In this review, evidence of the antioxidant effects of MSCs in in vivo and in vitro models is explored and potential mechanisms of these effects are discussed. These include direct scavenging of free radicals, promoting endogenous antioxidant defenses, immunomodulation via reactive oxygen species suppression, altering mitochondrial bioenergetics, and donating functional mitochondria to damaged cells. Modulation of the redox environment and oxidative stress by MSCs can mediate their anti-inflammatory and cytoprotective properties and may offer an explanation to the diversity in disease models treatable by MSCs and how these mechanisms may be conserved between species.
Topics: Animals; Antioxidants; Disease Models, Animal; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Oxidative Stress; Reactive Oxygen Species
PubMed: 32497410
DOI: 10.1002/sctm.19-0446 -
Nature Biotechnology Mar 2014The diverse immunomodulatory properties of mesenchymal stem/stromal cells (MSCs) may be exploited for treatment of a multitude of inflammatory conditions. MSCs have long... (Review)
Review
The diverse immunomodulatory properties of mesenchymal stem/stromal cells (MSCs) may be exploited for treatment of a multitude of inflammatory conditions. MSCs have long been reported to be hypoimmunogenic or 'immune privileged'; this property is thought to enable MSC transplantation across major histocompatibility barriers and the creation of off-the-shelf therapies consisting of MSCs grown in culture. However, recent studies describing generation of antibodies against and immune rejection of allogeneic donor MSCs suggest that MSCs may not actually be immune privileged. Nevertheless, whether rejection of donor MSCs influences the efficacy of allogeneic MSC therapies is not known, and no definitive clinical advantage of autologous MSCs over allogeneic MSCs has been demonstrated to date. Although MSCs may exert therapeutic function through a brief 'hit and run' mechanism, protecting MSCs from immune detection and prolonging their persistence in vivo may improve clinical outcomes and prevent patient sensitization toward donor antigens.
Topics: Animals; Biomedical Research; Clinical Trials as Topic; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Transplantation, Homologous
PubMed: 24561556
DOI: 10.1038/nbt.2816 -
International Journal of Molecular... Aug 2014Mesenchymal stem cells (MSCs) are multipotent stem cells that give rise to various cell types of the mesodermal germ layer. Because of their unique ability to home in on... (Review)
Review
Mesenchymal stem cells (MSCs) are multipotent stem cells that give rise to various cell types of the mesodermal germ layer. Because of their unique ability to home in on injured and cancerous tissues, MSCs are of great potential in regenerative medicine. MSCs also contribute to reparative processes in different pathological conditions, including cardiovascular diseases and cancer. However, many studies have shown that only a small proportion of transplanted MSCs can actually survive and be incorporated into host tissues. The effects of MSCs cannot be fully explained by their number. Recent discoveries suggest that microparticles (MPs) derived from MSCs may be important for the physiological functions of their parent. Though the physiological role of MSC-MPs is currently not well understood, inspiring results indicate that, in tissue repair and anti-cancer therapy, MSC-MPs have similar pro-regenerative and protective properties as their cellular counterparts. Thus, MSC-MPs represent a promising approach that may overcome the obstacles and risks associated with the use of native or engineered MSCs.
Topics: Cell-Derived Microparticles; Humans; Mesenchymal Stem Cells
PubMed: 25196436
DOI: 10.3390/ijms150814348 -
Biotechnology Journal Jan 2016Human mesenchymal stem cells (hMSCs) have emerged as an important cell type in cell therapy and tissue engineering. In these applications, maintaining the therapeutic... (Review)
Review
Human mesenchymal stem cells (hMSCs) have emerged as an important cell type in cell therapy and tissue engineering. In these applications, maintaining the therapeutic properties of hMSCs requires tight control of the culture environments and the structural cell organizations. Bioreactor systems are essential tools to achieve these goals in the clinical-scale expansion and tissue engineering applications. This review summarizes how different bioreactors provide cues to regulate the structure and the chemico-mechanical microenvironment of hMSCs with a focus on 3D organization. In addition to conventional bioreactors, recent advances in microfluidic bioreactors as a novel approach to better control the hMSC microenvironment are also discussed. These advancements highlight the key role of bioreactor systems in preserving hMSC's functional properties by providing dynamic and temporal regulation of in vitro cellular microenvironment.
Topics: Bioreactors; Cell Culture Techniques; Cells, Cultured; Humans; Mesenchymal Stem Cells; Microfluidics; Tissue Engineering
PubMed: 26696441
DOI: 10.1002/biot.201500191 -
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 -
Current Opinion in Biotechnology Oct 2009Mesenchymal stem cell (MSC)-based therapeutics are showing significant benefit in multiple clinical trials conducted by both academic and commercial organizations, but... (Review)
Review
Mesenchymal stem cell (MSC)-based therapeutics are showing significant benefit in multiple clinical trials conducted by both academic and commercial organizations, but obstacles remain for their large-scale commercial implementation. Recent studies have attempted to optimize MSC-based therapeutics by either enhancing their potency or increasing their delivery to target tissues. Overexpression of trophic factors or in vitro exposure to potency-enhancing factors are two approaches that are demonstrating success in preclinical animal models. Delivery enhancement strategies involving tissue-specific cytokine pathways or binding sites are also showing promise. Each of these strategies has its own set of distinct advantages and disadvantages when viewed with a mindset of ultimate commercialization and clinical utility.
Topics: Animals; Cell Movement; Gene Transfer Techniques; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Organ Specificity
PubMed: 19783424
DOI: 10.1016/j.copbio.2009.08.009 -
Transplantation Jun 2015
Review
Topics: Antigens, CD; Cell Differentiation; Cell Separation; Cell- and Tissue-Based Therapy; Cellular Senescence; Clinical Trials as Topic; Humans; Immunomodulation; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Paracrine Communication; Regenerative Medicine
PubMed: 26035274
DOI: 10.1097/TP.0000000000000734 -
Stem Cell Reviews and Reports Aug 2014There is significant interest in the use of mesenchymal stem cells (MSCs) as a potential therapeutic modality in disease and disorder, particularly those with an... (Review)
Review
There is significant interest in the use of mesenchymal stem cells (MSCs) as a potential therapeutic modality in disease and disorder, particularly those with an inflammation-based component such as coronary, renal and hepatic diseases. While there is no question that MSCs possess the capability to manipulate an ongoing inflammatory injury, the recruitment of these cells to injured sites is generally poor, and thus, open to manipulation. Enhancing the localised recruitment of MSCs to injured tissues may enhance the efficiency and efficacy of this mode of therapy. A number of techniques exist in the literature to improve the recruitment of MSCs to injured tissues, including the use of cytokines, chemical modifications and coating with either synthetic or biological particles. In addition to enhancing MSC recruitment, there is an increasing body of work examining techniques which may enhance the anti-inflammatory activity of these cells. This review will summarise the literature around these topics. This first section of this review summarises the current literature with regard to MSC homing and their recruitment during conditions of injury. In relation to the anti-inflammatory activity of MSCs, the role of systemic versus local activity will be discussed. The second part of the review focuses on the role of pretreatments in MSC therapy and how these may have potential for not only enhancing the recruitment of MSCs, but also their anti-inflammatory capabilities. In summary, it is clear that there is significant potential to improve the efficiency of MSC therapy and the techniques discussed in this review may be central to this in the future.
Topics: Animals; Cell Adhesion; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Tissue Engineering
PubMed: 24752328
DOI: 10.1007/s12015-014-9510-7