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Stem Cell Research & Therapy Feb 2022Cell therapy, particularly mesenchymal stem/stromal (MSC) therapy, has been investigated for a wide variety of disease indications, particularly those with inflammatory... (Review)
Review
Cell therapy, particularly mesenchymal stem/stromal (MSC) therapy, has been investigated for a wide variety of disease indications, particularly those with inflammatory pathologies. However, recently it has become evident that the MSC is far from a panacea. In this review we will look at current and future strategies that might overcome limitations in efficacy. Many of these take their inspiration from stem cell niche and the mechanism of MSC action in response to the injury microenvironment, or from previous gene therapy work which can now benefit from the added longevity and targeting ability of a live cell vector. We will also explore the nascent field of extracellular vesicle therapy and how we are already seeing enhancement protocols for this exciting new drug. These enhanced MSCs will lead the way in more difficult to treat diseases and restore potency where donors or manufacturing practicalities lead to diminished MSC effect.
Topics: Cell- and Tissue-Based Therapy; Extracellular Vesicles; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Signal Transduction; Stem Cell Niche
PubMed: 35189962
DOI: 10.1186/s13287-022-02747-w -
International Journal of Molecular... Jan 2021Stem cells including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and adult stem cells (ASCs) are able to repair/replace damaged or degenerative... (Review)
Review
Stem cells including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and adult stem cells (ASCs) are able to repair/replace damaged or degenerative tissues and improve functional recovery in experimental model and clinical trials. However, there are still many limitations and unresolved problems regarding stem cell therapy in terms of ethical barriers, immune rejection, tumorigenicity, and cell sources. By reviewing recent literatures and our related works, human amnion-derived stem cells (hADSCs) including human amniotic mesenchymal stem cells (hAMSCs) and human amniotic epithelial stem cells (hAESCs) have shown considerable advantages over other stem cells. In this review, we first described the biological characteristics and advantages of hADSCs, especially for their high pluripotency and immunomodulatory effects. Then, we summarized the therapeutic applications and recent progresses of hADSCs in treating various diseases for preclinical research and clinical trials. In addition, the possible mechanisms and the challenges of hADSCs applications have been also discussed. Finally, we highlighted the properties of hADSCs as a promising source of stem cells for cell therapy and regenerative medicine and pointed out the perspectives for the directions of hADSCs applications clinically.
Topics: Amnion; Cell Differentiation; Cell- and Tissue-Based Therapy; Epithelial Cells; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Regenerative Medicine
PubMed: 33478081
DOI: 10.3390/ijms22020970 -
International Journal of Molecular... Apr 2024During the last three decades, mesenchymal stem/stromal cells (MSCs) were extensively studied, and are mainly considered within the setting of their regenerative and...
During the last three decades, mesenchymal stem/stromal cells (MSCs) were extensively studied, and are mainly considered within the setting of their regenerative and immunomodulatory properties in tissue regeneration [...].
Topics: Mesenchymal Stem Cells; Humans; Regeneration; Animals; Mesenchymal Stem Cell Transplantation; Tissue Engineering; Regenerative Medicine; Cell Differentiation
PubMed: 38732156
DOI: 10.3390/ijms25094937 -
Biological Chemistry Dec 2019Recent evidence indicates that the plasticity of preexisting hepatocytes and bile duct cells is responsible for the appearance of intermediate progenitor cells capable... (Review)
Review
Recent evidence indicates that the plasticity of preexisting hepatocytes and bile duct cells is responsible for the appearance of intermediate progenitor cells capable of restoring liver mass after injury without the need of a stem cell compartment. However, mesenchymal stem cells (MSCs) exist in all organs and are associated with blood vessels which represent their perivascular stem cell niche. MSCs are multipotent and can differentiate into several cell types and are known to support regenerative processes by the release of immunomodulatory and trophic factors. In the liver, the space of Disse constitutes a stem cell niche that harbors stellate cells as liver resident MSCs. This perivascular niche is created by extracellular matrix proteins, sinusoidal endothelial cells, liver parenchymal cells and sympathetic nerve endings and establishes a microenvironment that is suitable to maintain stellate cells and to control their fate. The stem cell niche integrity is important for the behavior of stellate cells in the normal, regenerative, aged and diseased liver. The niche character of the space of Disse may further explain why the liver can become an organ of extra-medullar hematopoiesis and why this organ is frequently prone to tumor metastasis.
Topics: Bile Ducts; Cell Differentiation; Endothelial Cells; Hematopoiesis; Hepatocytes; Humans; Liver; Liver Regeneration; Mesenchymal Stem Cells; Stem Cell Niche; Stem Cells
PubMed: 31318687
DOI: 10.1515/hsz-2019-0283 -
Global Heart 2022Although tremendous progress has been made in conventional treatment for ischemic heart disease, it still remains a major cause of death and disability. Cell-based... (Review)
Review
Although tremendous progress has been made in conventional treatment for ischemic heart disease, it still remains a major cause of death and disability. Cell-based therapeutics holds an exciting frontier of research for complete cardiac recuperation. The capacity of diverse stem and progenitor cells to stimulate cardiac renewal has been analysed, with promising results in both pre-clinical and clinical trials. Mesenchymal stem cells have been ascertained to have regenerative ability via a variety of mechanisms, including differentiation from the mesoderm lineage, immunomodulatory properties, and paracrine effects. Also, their availability, maintenance, and ability to replenish endogenous stem cell niches have rendered them suitable for front-line research. This review schemes to outline the use of mesenchymal stem cell therapeutics for ischemic heart disease, their characteristics, the potent mechanisms of mesenchymal stem cell-based heart regeneration, and highlight preclinical data. Additionally, we discuss the results of the clinical trials to date as well as ongoing clinical trials on ischemic heart disease.
Topics: Cell Differentiation; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Myocardial Ischemia
PubMed: 35342702
DOI: 10.5334/gh.1098 -
International Journal of Molecular... Oct 2021Regenerative medicine is concerned with the investigation of therapeutic agents that can be used to promote the process of regeneration after injury or in different... (Review)
Review
Regenerative medicine is concerned with the investigation of therapeutic agents that can be used to promote the process of regeneration after injury or in different diseases. Mesenchymal stem/stromal cells (MSCs) and their secretome-including extracellular vesicles (EVs) are of great interest, due to their role in tissue regeneration, immunomodulatory capacity and low immunogenicity. So far, clinical studies are not very conclusive as they show conflicting efficacies regarding the use of MSCs. An additional process possibly involved in regeneration might be cell fusion. This process occurs in both a physiological and a pathophysiological context and can be affected by immune response due to inflammation. In this review the role of MSCs and cell fusion in tissue regeneration is discussed.
Topics: Bone Diseases; Cell Differentiation; Cell Fusion; Extracellular Vesicles; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Neoplasms; Paracrine Communication; Regenerative Medicine
PubMed: 34681639
DOI: 10.3390/ijms222010980 -
Frontiers in Immunology 2020Studies over the last couple of decades have shown that hematopoietic stem cells (HSCs) are critically dependent on cytokines such as Stem Cell Factor and other signals... (Review)
Review
Studies over the last couple of decades have shown that hematopoietic stem cells (HSCs) are critically dependent on cytokines such as Stem Cell Factor and other signals provided by bone marrow niches comprising of mesenchymal stem and progenitor cells (MSPCs) and endothelial cells (ECs). Because of their critical roles in HSC maintenance the niches formed by MSPCs and ECs are commonly referred to as HSC niches. For the most part, the signals required for HSC maintenance act in a short-range manner, which imposes the necessity for directional and positional cues in order for HSCs to localize and be retained properly in stem cell niches. The chemokine CXCL12 and its Gαi protein coupled receptor CXCR4, besides promoting HSC quiescence directly, also play instrumental roles in enabling HSCs to access bone marrow stem cell niches. Recent studies have revealed, however, that HSC niches also provide a constellation of hematopoietic cytokines that are critical for the production of most, if not all, blood cell types. Some hematopoietic cytokines, namely IL-7 and IL-15 produced by HSC niches, are not only required for lymphopoiesis but are also essential for memory T cell maintenance. Consequently, hematopoietic progenitors and differentiated immune cells, such as memory T cell subsets, also depend on the CXCL12/CXCR4 axis for migration into bone marrow and interactions with MSPCs and ECs. Similarly, subsets of antibody-secreting plasma cells also reside in close association with CXCL12-producing MSPCs in the bone marrow and require the CXCR4/CXCL12 axis for survival and long-term maintenance. Collectively, these studies demonstrate a broad range of key physiological roles, spanning blood cell production and maintenance of immunological memory, that are orchestrated by stem cell niches through a common and simple mechanism: CXCL12/CXCR4-mediated cell recruitment followed by receipt of a maintenance and/or instructive signal. A fundamental flaw of this type of cellular organization is revealed by myeloid and lymphoid leukemias, which target stem cell niches and induce profound transcriptomic changes that result in reduced hematopoietic activity and altered mesenchymal cell differentiation.
Topics: Animals; Endothelial Cells; Hematopoietic Stem Cells; Humans; Immunologic Memory; Mesenchymal Stem Cells; Signal Transduction; Stem Cell Niche
PubMed: 33324418
DOI: 10.3389/fimmu.2020.600127 -
International Journal of Oral Science Feb 2024Mammalian teeth, developing inseparable from epithelial-mesenchymal interaction, come in many shapes and the key factors governing tooth morphology deserve to be...
Mammalian teeth, developing inseparable from epithelial-mesenchymal interaction, come in many shapes and the key factors governing tooth morphology deserve to be answered. By merging single-cell RNA sequencing analysis with lineage tracing models, we have unearthed a captivating correlation between the contrasting morphology of mouse molars and the specific presence of PRX1 cells within M1. These PRX1 cells assume a profound responsibility in shaping tooth morphology through a remarkable divergence in dental mesenchymal cell proliferation. Deeper into the mechanisms, we have discovered that Wnt5a, bestowed by mesenchymal PRX1 cells, stimulates mesenchymal cell proliferation while orchestrating molar morphogenesis through WNT signaling pathway. The loss of Wnt5a exhibits a defect phenotype similar to that of siPrx1. Exogenous addition of WNT5A can successfully reverse the inhibited cell proliferation and consequent deviant appearance exhibited in Prx1-deficient tooth germs. These findings bestow compelling evidence of PRX1-positive mesenchymal cells to be potential target in regulating tooth morphology.
Topics: Animals; Mice; Mesenchymal Stem Cells; Molar; Morphogenesis; Tooth Germ
PubMed: 38369512
DOI: 10.1038/s41368-024-00277-0 -
Cells Dec 2022Mesenchymal stem cells (MSCs) are non-hematopoietic progenitor cells with self-renewal ability and multipotency of osteogenic, chondrogenic, and adipogenic... (Review)
Review
Mesenchymal stem cells (MSCs) are non-hematopoietic progenitor cells with self-renewal ability and multipotency of osteogenic, chondrogenic, and adipogenic differentiation. MSCs have appeared as a promising approach for tissue regeneration and immune therapies, which are attributable not only to their differentiation into the desired cells but also to their paracrine secretion. MSC-sourced secretome consists of soluble components including growth factors, chemokines, cytokines, and encapsulated extracellular vesicles (EVs). Apoptotic bodies (ABs) are large EVs (diameter 500𠀓2000 nm) harboring a variety of cellular components including microRNA, mRNA, DNA, protein, and lipids related to the characteristics of the originating cell, which are generated during apoptosis. The released ABs as well as the genetic information they carry are engulfed by target cells such as macrophages, dendritic cells, epithelial cells, and fibroblasts, and subsequently internalized and degraded in the lysosomes, suggesting their ability to facilitate intercellular communication. In this review, we discuss the current understanding of the biological functions and therapeutic potential of MSC-derived ABs, including immunomodulation, tissue regeneration, regulation of inflammatory response, and drug delivery system.
Topics: Extracellular Vesicles; Mesenchymal Stem Cells; Cell Differentiation; Immunomodulation; Apoptosis
PubMed: 36497136
DOI: 10.3390/cells11233879 -
Scientific Reports Apr 2021In recent years, 3D cell culture models such as spheroid or organoid technologies have known important developments. Many studies have shown that 3D cultures exhibit...
In recent years, 3D cell culture models such as spheroid or organoid technologies have known important developments. Many studies have shown that 3D cultures exhibit better biomimetic properties compared to 2D cultures. These properties are important for in-vitro modeling systems, as well as for in-vivo cell therapies and tissue engineering approaches. A reliable use of 3D cellular models still requires standardized protocols with well-controlled and reproducible parameters. To address this challenge, a robust and scaffold-free approach is proposed, which relies on multi-trap acoustic levitation. This technology is successfully applied to Mesenchymal Stem Cells (MSCs) maintained in acoustic levitation over a 24-h period. During the culture, MSCs spontaneously self-organized from cell sheets to cell spheroids with a characteristic time of about 10 h. Each acoustofluidic chip could contain up to 30 spheroids in acoustic levitation and four chips could be ran in parallel, leading to the production of 120 spheroids per experiment. Various biological characterizations showed that the cells inside the spheroids were viable, maintained the expression of their cell surface markers and had a higher differentiation capacity compared to standard 2D culture conditions. These results open the path to long-time cell culture in acoustic levitation of cell sheets or spheroids for any type of cells.
Topics: Acoustics; Cell Culture Techniques; Cell Differentiation; Cell Proliferation; Cell Survival; Cells, Cultured; Fluoresceins; Humans; Mesenchymal Stem Cells; Propidium; Spheroids, Cellular; Time Factors; Tissue Engineering
PubMed: 33863936
DOI: 10.1038/s41598-021-87459-6