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Stem Cell Reviews and Reports Oct 2018
Topics: Bone Marrow Cells; Humans; Mesenchymal Stem Cells; Peripheral Blood Stem Cells
PubMed: 30088212
DOI: 10.1007/s12015-018-9842-9 -
Critical Reviews in Oncology/hematology Jan 2017The majority of human tumours are comprised of cancerous epithelial cells that coexist with a multitude of different cell types and extracellular matrix components... (Review)
Review
The majority of human tumours are comprised of cancerous epithelial cells that coexist with a multitude of different cell types and extracellular matrix components creating the cancer microenvironment. Cancer-associated fibroblasts (CAFs) are the most abundant mesenchymal cell types present within most human carcinomas. Recent evidence suggests that nutrient deprived epithelial cancer cells are able to survive these conditions, as a result of their ability to undergo extensive metabolic reprogramming and exploit the metabolic capacities of surrounding CAFs. Although several studies support the role of CAFs in tumour progression and metastasis, the molecular mechanisms underlying this pro-tumourigenic interaction remains to be elucidated. This review will discuss the complex metabolic interaction that exists between epithelial cancer cells and CAF's: focussing primarily on their functional role in tumour progression, metastasis and chemotherapeutic resistance. Attempts are made at delineating the molecular mechanisms underlying this pro-tumourigenic interaction, and potential CAF-based targets are suggested.
Topics: Animals; Cell Survival; Fibroblasts; Humans; Mesenchymal Stem Cells; Neoplasms; Tumor Microenvironment
PubMed: 28010894
DOI: 10.1016/j.critrevonc.2016.11.010 -
Development, Growth & Differentiation Jun 2016Mesenchymal stem cells (MSCs) are defined as progenitor cells that give rise to a number of unique, differentiated mesenchymal cell types. This concept has progressively... (Review)
Review
Mesenchymal stem cells (MSCs) are defined as progenitor cells that give rise to a number of unique, differentiated mesenchymal cell types. This concept has progressively evolved towards an all-encompassing concept including multipotent perivascular cells of almost any tissue. In central nervous system, pericytes are involved in blood-brain barrier, and angiogenesis and vascular tone regulation. They form the neurovascular unit (NVU) together with endothelial cells, astrocytes and neurons. This functional structure provides an optimal microenvironment for neural proliferation in the adult brain. Neurovascular niche include both diffusible signals and direct contact with endothelial and pericytes, which are a source of diffusible neurotrophic signals that affect neural precursors. Therefore, MSCs/pericyte properties such as differentiation capability, as well as immunoregulatory and paracrine effects make them a potential resource in regenerative medicine.
Topics: Animals; Astrocytes; Blood-Brain Barrier; Cell Differentiation; Endothelial Cells; Humans; Mesenchymal Stem Cells; Neural Stem Cells; Neurons
PubMed: 27273235
DOI: 10.1111/dgd.12296 -
IUBMB Life Feb 2020The endoplasmic reticulum (ER) receives unfolded proteins predestined for the secretory pathway or to be incorporated as transmembrane proteins. The ER has to... (Review)
Review
The endoplasmic reticulum (ER) receives unfolded proteins predestined for the secretory pathway or to be incorporated as transmembrane proteins. The ER has to accommodate the proper folding and glycosylation of these proteins and also to properly incorporate transmembrane proteins. However, under various circumstances, the proteins shuttling through the ER can be misfolded and undergo aggregation, which causes activation of the unfolded protein response (UPR). The UPR is mediated through three primary pathways: activating transcription factor-6, inositol-requiring enzyme-1 (IRE1), and PKR-like endoplasmic reticulum kinase, which up-regulate ER folding chaperones and temporarily suppress protein translation. The UPR can be both cytoprotective and/or cytotoxic depending on the duration of UPR activation and the type of host cell. Proteostasis controls stem cell function, while stress responses affect stem cell identity and differentiation. The present review aimed to explore and discuss the effects of the UPR pathways on mesenchymal stem cells.
Topics: Animals; Endoplasmic Reticulum; Humans; Mesenchymal Stem Cells; Protein Biosynthesis; Signal Transduction; Unfolded Protein Response
PubMed: 31444957
DOI: 10.1002/iub.2154 -
Reviews in the Neurosciences Nov 2019Traumatic brain injury (TBI) is a major cause of injury-related mortality and morbidity in the USA and around the world. The survivors may suffer from cognitive and... (Review)
Review
Traumatic brain injury (TBI) is a major cause of injury-related mortality and morbidity in the USA and around the world. The survivors may suffer from cognitive and memory deficits, vision and hearing loss, movement disorders, and different psychological problems. The primary insult causes neuronal damage and activates astrocytes and microglia which evokes immune responses causing further damage to the brain. Clinical trials of drugs to recover the neuronal loss are not very successful. Regenerative approaches for TBI using mesenchymal stem cells (MSCs) seem promising. Results of preclinical research have shown that transplantation of MSCs reduced secondary neurodegeneration and neuroinflammation, promoted neurogenesis and angiogenesis, and improved functional outcome in the experimental animals. The functional improvement is not necessarily related to cell engraftment; rather, immunomodulation by molecular factors secreted by MSCs is responsible for the beneficial effects of this therapy. However, MSC therapy has a few drawbacks including tumor formation, which can be avoided by the use of MSC-derived exosomes. This review has focused on the research works published in the field of regenerative therapy using MSCs after TBI and its future direction.
Topics: Animals; Brain Injuries, Traumatic; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Regenerative Medicine; Translational Research, Biomedical
PubMed: 31203262
DOI: 10.1515/revneuro-2019-0002 -
Pulmonary Pharmacology & Therapeutics Dec 2014Pulmonary inflammation and tissue remodelling are common elements of chronic respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD),... (Review)
Review
Pulmonary inflammation and tissue remodelling are common elements of chronic respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and pulmonary hypertension (PH). In disease, pulmonary mesenchymal cells not only contribute to tissue remodelling, but also have an important role in pulmonary inflammation. This review will describe the immunomodulatory functions of pulmonary mesenchymal cells, such as airway smooth muscle (ASM) cells and lung fibroblasts, in chronic respiratory disease. An important theme of the review is that pulmonary mesenchymal cells not only respond to inflammatory mediators, but also produce their own mediators, whether pro-inflammatory or pro-resolving, which influence the quantity and quality of the lung immune response. The notion that defective pro-inflammatory or pro-resolving signalling in these cells potentially contributes to disease progression is also discussed. Finally, the concept of specifically targeting pulmonary mesenchymal cell immunomodulatory function to improve therapeutic control of chronic respiratory disease is considered.
Topics: Airway Remodeling; Animals; Humans; Lung Diseases; Mesenchymal Stem Cells; Pneumonia
PubMed: 24657485
DOI: 10.1016/j.pupt.2014.03.001 -
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 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 -
Current Opinion in Hematology Jul 2016The bone marrow niche is increasingly recognized as heterogeneous with specific subtypes of mesenchymal niche cells governing the development or homeostasis of selective... (Review)
Review
PURPOSE OF REVIEW
The bone marrow niche is increasingly recognized as heterogeneous with specific subtypes of mesenchymal niche cells governing the development or homeostasis of selective parenchymal hematopoietic subsets. The present review outlines recent efforts in dissecting these microniches regulated by unique cell pairings within the bone marrow and provides an overview of how the bone marrow orchestrates multiple facets of hematopoiesis.
RECENT FINDINGS
Recent advancement in technologies has significantly improved our understanding of the cellular and molecular constituents that contribute to regulation of hematopoiesis and to maintenance of the hematopoietic stem cells (HSCs). Transgenic mouse models that enable endogenous cell deletion or lineage tracing, coupled with advanced intravital microscopy has identified several mesenchymal cell types, including the osteolineage cells, megakaryocytes, macrophages, perivascular cells, and Schwann cells, to be indispensible regulators of hematopoiesis. These niche cells, when perturbed, each caused very specific hematopoietic consequences including impairment in B-cell maturation, T lineage development, erythropoiesis, and impact different aspects of HSC behavior such as quiescence, mobilization, and response to acute stress signals.
SUMMARY
The emerging concept is that the bone marrow environment is composed of multiple microniches, each consisting of unique pairing of distinct supportive stromal cells with distinct hematopoietic subtypes to regulate a particular branch of hematopoietic cell process. The bone marrow can be viewed as a carrier with subcompartments tailored to support different hematopoietic activities.
Topics: Animals; Bone Marrow Cells; Cell Communication; Cell Cycle; Cell Differentiation; Cell Movement; Erythropoiesis; Hematopoiesis; Hematopoietic Stem Cells; Humans; Lymphoid Progenitor Cells; Lymphopoiesis; Macrophages; Megakaryocytes; Mesenchymal Stem Cells; Osteogenesis; Stem Cell Niche; Stress, Physiological; Sympathetic Nervous System
PubMed: 27177311
DOI: 10.1097/MOH.0000000000000265 -
Frontiers of Medicine Apr 2019As a promising candidate seed cell type in regenerative medicine, mesenchymal stem cells (MSCs) have attracted considerable attention. The unique capacity of MSCs to... (Review)
Review
As a promising candidate seed cell type in regenerative medicine, mesenchymal stem cells (MSCs) have attracted considerable attention. The unique capacity of MSCs to exert a regulatory effect on immunity in an autologous/allergenic manner makes them an attractive therapeutic cell type for immune disorders. In this review, we discussed the current knowledge of and advances in MSCs, including its basic biological properties, i.e., multilineage differentiation, secretome, and immunomodulation. Specifically, on the basis of our previous work, we proposed three new concepts of MSCs, i.e., "subtotipotent stem cell" hypothesis, MSC system, and "Yin and Yang" balance of MSC regulation, which may bring new insights into our understanding of MSCs. Furthermore, we analyzed data from the Clinical Trials database ( http://clinicaltrials.gov ) on registered clinical trials using MSCs to treat a variety of immune diseases, such as graft-versus-host disease, systemic lupus erythematosus, and multiple sclerosis. In addition, we highlighted MSC clinical trials in China and discussed the challenges and future directions in the field of MSC clinical application.
Topics: Cell Differentiation; Humans; Immune System Diseases; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Randomized Controlled Trials as Topic; Regenerative Medicine
PubMed: 30062557
DOI: 10.1007/s11684-018-0627-y