scholarly journals Potential Therapies by Stem Cell-Derived Exosomes in CNS Diseases: Focusing on the Neurogenic Niche

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Alejandro Luarte ◽  
Luis Federico Bátiz ◽  
Ursula Wyneken ◽  
Carlos Lafourcade
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neurodegenerative Disorders ◽  
Cell Types ◽  
Therapeutic Benefit ◽  
Brain Diseases ◽  
Specific Cell ◽  
Novel Approaches

Neurodegenerative disorders are one of the leading causes of death and disability and one of the biggest burdens on health care systems. Novel approaches using various types of stem cells have been proposed to treat common neurodegenerative disorders such as Alzheimer’s Disease, Parkinson’s Disease, or stroke. Moreover, as the secretome of these cells appears to be of greater benefit compared to the cells themselves, the extracellular components responsible for its therapeutic benefit have been explored. Stem cells, as well as most cells, release extracellular vesicles such as exosomes, which are nanovesicles able to target specific cell types and thus to modify their function by delivering proteins, lipids, and nucleic acids. Exosomes have recently been testedin vivoandin vitroas therapeutic conveyors for the treatment of diseases. As such, they could be engineered to target specific populations of cells within the CNS. Considering the fact that many degenerative brain diseases have an impact on adult neurogenesis, we discuss how the modulation of the adult neurogenic niches may be a therapeutic target of stem cell-derived exosomes. These novel approaches should be examined in cellular and animal models to provide better, more effective, and specific therapeutic tools in the future.

scholarly journals Human Organoids for Predictive Toxicology Research and Drug Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Toshikatsu Matsui ◽  
Tadahiro Shinozawa
Keyword(s):  
Stem Cells ◽  
Drug Development ◽  
Disease Modeling ◽  
Cell Types ◽  
Underlying Disease ◽  
Future Research ◽  
Specific Cell ◽  
Predictive Toxicology

Organoids are three-dimensional structures fabricated in vitro from pluripotent stem cells or adult tissue stem cells via a process of self-organization that results in the formation of organ-specific cell types. Human organoids are expected to mimic complex microenvironments and many of the in vivo physiological functions of relevant tissues, thus filling the translational gap between animals and humans and increasing our understanding of the mechanisms underlying disease and developmental processes. In the last decade, organoid research has attracted increasing attention in areas such as disease modeling, drug development, regenerative medicine, toxicology research, and personalized medicine. In particular, in the field of toxicology, where there are various traditional models, human organoids are expected to blaze a new path in future research by overcoming the current limitations, such as those related to differences in drug responses among species. Here, we discuss the potential usefulness, limitations, and future prospects of human liver, heart, kidney, gut, and brain organoids from the viewpoints of predictive toxicology research and drug development, providing cutting edge information on their fabrication methods and functional characteristics.

Mesenchymal stem cell adhesion to cardiac microvascular endothelium: activators and mechanisms

2006 ◽  
Vol 290 (4) ◽  
pp. H1370-H1377 ◽  
Author(s):  
Vincent F. M. Segers ◽  
Ivan Van Riet ◽  
Luc J. Andries ◽  
Katrien Lemmens ◽  
Marc J. Demolder ◽  
...  
Keyword(s):  
Stem Cells ◽  
Shear Stress ◽  
Stem Cell ◽  
Cell Types ◽  
Microvascular Endothelium ◽  
Rat Hearts ◽  
Tnf Α ◽  
Stromal Cell Derived Factor

Circulating stem cells home within the myocardium, probably as the first step of a tissue regeneration process. This step requires adhesion to cardiac microvascular endothelium (CMVE). In this study, we studied mechanisms of adhesion between CMVE and mesenchymal stem cells (MSCs). Adhesion was studied in vitro and in vivo. Isolated 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate-labeled rat MSCs were allowed to adhere to cultured CMVE in static and dynamic conditions. Either CMVE or MSCs were pretreated with cytokines [IL-1β, IL-3, IL-6, stem cell factor, stromal cell-derived factor-1, or TNF-α, 10 ng/ml]. Control or TNF-α-treated MSCs were injected intracavitarily in rat hearts in vivo. In baseline in vitro conditions, the number of MSCs that adhered to CMVE was highly dependent on the flow rate of the superfusing medium but remained significant at venous and capillary shear stress amplitudes. Activation of both CMVE and MSCs with TNF-α or IL-1β before adhesion concentration dependently increased adhesion of MSCs at each studied level of shear stress. Consistently, in vivo, activation of MSCs with TNF-α before injection significantly enhanced cardiac homing of MSCs. TNF-α-induced adhesion could be completely blocked by pretreating either CMVE or MSCs with anti-VCAM-1 monoclonal antibodies but not by anti-ICAM-1 antibodies. Adhesion of circulating MSCs in the heart appears to be an endothelium-dependent process and is sensitive to modulation by activators of both MSCs and endothelium. Inflammation and the expression of VCAM-1 but not ICAM-1 on both cell types have a regulatory effect on MSC homing in the heart.

scholarly journals Organotypic Cocultures of Human Pluripotent Stem Cell Derived-Neurons with Mammalian Inner Ear Hair Cells and Cochlear Nucleus Slices

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Tomoko Hyakumura ◽  
Stuart McDougall ◽  
Sue Finch ◽  
Karina Needham ◽  
Mirella Dottori ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Inner Ear ◽  
Hair Cells ◽  
Cochlear Nucleus ◽  
Cell Types ◽  
Quantitative Evidence ◽  
Brainstem Slice

Stem cells have been touted as a source of potential replacement neurons for inner ear degeneration for almost two decades now; yet to date, there are few studies describing the use of human pluripotent stem cells (hPSCs) for this purpose. If stem cell therapies are to be used clinically, it is critical to validate the usefulness of hPSC lines in vitro and in vivo. Here, we present the first quantitative evidence that differentiated hPSC-derived neurons that innervate both the inner ear hair cells and cochlear nucleus neurons in coculture, with significantly more new synaptic contacts formed on target cell types. Nascent contacts between stem cells and hair cells were immunopositive for both synapsin I and VGLUT1, closely resembling expression of these puncta in endogenous postnatal auditory neurons and control cocultures. When hPSCs were cocultured with cochlear nucleus brainstem slice, significantly greater numbers of VGLUT1 puncta were observed in comparison to slice alone. New VGLUT1 puncta in cocultures with cochlear nucleus slice were not significantly different in size, only in quantity. This experimentation describes new coculture models for assessing auditory regeneration using well-characterised hPSC-derived neurons and highlights useful methods to quantify the extent of innervation on different cell types in the inner ear and brainstem.

scholarly journals Divergence in chondrogenic potential between in vitro and in vivo of adipose- and synovial-stem cells from mouse and human

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chijimatsu Ryota ◽  
Miwa Satoshi ◽  
Okamura Gensuke ◽  
Miyahara Junya ◽  
Tachibana Naohiro ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Transforming Growth Factor ◽  
Cartilage Regeneration ◽  
Cell Types ◽  
Cartilage Defects ◽  
Chondrogenic Potential ◽  
Tgfβ Receptors

Abstract Background Somatic stem cell transplantation has been performed for cartilage injury, but the reparative mechanisms are still conflicting. The chondrogenic potential of stem cells are thought as promising features for cartilage therapy; however, the correlation between their potential for chondrogenesis in vitro and in vivo remains undefined. The purpose of this study was to investigate the intrinsic chondrogenic condition depends on cell types and explore an indicator to select useful stem cells for cartilage regeneration. Methods The chondrogenic potential of two different stem cell types derived from adipose tissue (ASCs) and synovium (SSCs) of mice and humans was assessed using bone morphogenic protein-2 (BMP2) and transforming growth factor-β1 (TGFβ1). Their in vivo chondrogenic potential was validated through transplantation into a mouse osteochondral defect model. Results All cell types showed apparent chondrogenesis under the combination of BMP2 and TGFβ1 in vitro, as assessed by the formation of proteoglycan- and type 2 collagen (COL2)-rich tissues. However, our results vastly differed with those observed following single stimulation among species and cell types; apparent chondrogenesis of mouse SSCs was observed with supplementation of BMP2 or TGFβ1, whereas chondrogenesis of mouse ASCs and human SSCs was observed with supplementation of BMP2 not TGFβ1. Human ASCs showed no obvious chondrogenesis following single stimulation. Mouse SSCs showed the formation of hyaline-like cartilage which had less fibrous components (COL1/3) with supplementation of TGFβ1. However, human cells developed COL1/3+ tissues with all treatments. Transcriptomic analysis for TGFβ receptors and ligands of cells prior to chondrogenic induction did not indicate their distinct reactivity to the TGFβ1 or BMP2. In the transplanted site in vivo, mouse SSCs formed hyaline-like cartilage (proteoglycan+/COL2+/COL1−/COL3−) but other cell types mainly formed COL1/3-positive fibrous tissues in line with in vitro reactivity to TGFβ1. Conclusion Optimal chondrogenic factors driving chondrogenesis from somatic stem cells are intrinsically distinct among cell types and species. Among them, the response to TGFβ1 may possibly represent the fate of stem cells when locally transplanted into cartilage defects.

scholarly journals The Use of Stem Cell-Derived Organoids in Disease Modeling: An Update

2021 ◽  
Vol 22 (14) ◽  
pp. 7667
Author(s):  
Joseph Azar ◽  
Hisham F. Bahmad ◽  
Darine Daher ◽  
Maya M. Moubarak ◽  
Ola Hadadeh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Disease Modeling ◽  
New Technology ◽  
Three Dimensional ◽  
Cell Types ◽  
Clinical Applications ◽  
In Vitro Drug Screening

Organoids represent one of the most important advancements in the field of stem cells during the past decade. They are three-dimensional in vitro culturing models that originate from self-organizing stem cells and can mimic the in vivo structural and functional specificities of body organs. Organoids have been established from multiple adult tissues as well as pluripotent stem cells and have recently become a powerful tool for studying development and diseases in vitro, drug screening, and host–microbe interaction. The use of stem cells—that have self-renewal capacity to proliferate and differentiate into specialized cell types—for organoids culturing represents a major advancement in biomedical research. Indeed, this new technology has a great potential to be used in a multitude of fields, including cancer research, hereditary and infectious diseases. Nevertheless, organoid culturing is still rife with many challenges, not limited to being costly and time consuming, having variable rates of efficiency in generation and maintenance, genetic stability, and clinical applications. In this review, we aim to provide a synopsis of pluripotent stem cell-derived organoids and their use for disease modeling and other clinical applications.

scholarly journals Mutational impact of culturing human pluripotent and adult stem cells

2018 ◽  
Author(s):  
Ewart Kuijk ◽  
Myrthe Jager ◽  
Bastiaan van der Roest ◽  
Mauro Locati ◽  
Arne Van Hoeck ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Base Pair ◽  
Adult Stem Cells ◽  
Cell Types ◽  
Ips Cells ◽  
Mutation Accumulation ◽  
Mutational Signature

AbstractGenetic changes acquired during in vitro culture pose a potential risk for the successful application of stem cells in regenerative medicine. To assess mutation accumulation risks induced by culturing, we determined genetic aberrations in individual human induced pluripotent stem cells (iPS cells) and adult stem cells (ASCs) by whole genome sequencing analyses. Individual iPS cells, intestinal ASCs and liver ASCs accumulated 3.5±0.5, 7.2±1.0 and 8.4±3.6 base substitutions per population doubling, respectively. The annual in vitro mutation accumulation rate of ASCs adds up to ∼1600 base pair substitutions, which is ∼40-fold higher than the in vivo rate of ∼40 base pair substitutions per year. Mutational analysis revealed a distinct in vitro induced mutational signature that is irrespective of stem cell type and distinct from the in vivo mutational signature. This in vitro signature is characterized by C to A changes that have previously been linked to oxidative stress conditions. Additionally, we observed stem cell-specific mutational signatures and differences in transcriptional strand bias, indicating differential activity of DNA repair mechanisms between stem cell types in culture. We demonstrate that the empirically defined mutation rates, spectra, and genomic distribution enable risk assessment by modelling the accumulation of specific oncogenic mutations during typical in vitro expansion, manipulation or screening experiments using human stem cells. Taken together, we have here for the first time accurately quantified and characterized in vitro mutation accumulation in human iPS cells and ASCs in a direct comparison. These results provide insights for further optimization of culture conditions for safe in vivo utilization of these cell types for regenerative purposes.

scholarly journals A comparative in vitro and in vivo study of osteogenicity by using two biomaterials and two human mesenchymal stem cell subtypes

2021 ◽  
Author(s):  
Lucile Fievet ◽  
Nicolas Serratrice ◽  
Benedicte Brulin ◽  
Laurent Giraudo ◽  
Julie Veran ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Bone Repair ◽  
Transcript Level ◽  
Cell Types ◽  
Human Mesenchymal Stem Cell ◽  
In Vivo Experiments

Bone repair induced by stem cells and biomaterials may represent an alternative to autologous bone grafting. Here, we compared the efficiency of two biomaterials - biphasic calcium phosphate (BCP) and bioactive glass (BG) - when loaded with either adult bone marrow mesenchymal stem cells (BM-MSCs) or newborn nasal ecto-mesenchymal stem cells (NE-MSCs), the latter being collected for further repair of lip cleft-associated bone loss. Both cell types display the typical stem cell surface markers CD73+/CD90+/CD105+/nestin, and exhibit the MSC-associated osteogenic, chondrogenic and adipogenic multipotency. NE-MSCs produce less collagen and alkaline phosphatase than BM-MSCs. At the transcript level, NE-MSCs express more abundantly three genes coding for bone sialoprotein, osteocalcin and osteopontin, while BM-MSCs produce extra copies of RUNX2. BM-MSCs and NE-MSCs adhere and survive on BCP and BG. In vivo experiments reveal that bone formation is only observed with BM-MSCs transplanted on BCP biomaterial.

scholarly journals Vascular Stem Cells in Vascular Remodeling and Diseases

2013 ◽  
Vol 5 (3) ◽  
pp. 151
Author(s):  
Anna Meiliana ◽  
Andi Wijaya
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Blood Vessels ◽  
Progenitor Cells ◽  
Tissue Expansion ◽  
Cell Types ◽  
Specific Cell ◽  
Vascular Stem Cells

BACKGROUND: Blood vessels are a source of stem and progenitor cells, which likely contribute to a variety of vascular processes and diseases. Emerging concepts in this field could influence therapeutic approaches to diseases of blood vessels such as atherosclerosis.CONTENT: Vascular Stem Cells (VSCs) field is only beginning to emerge, and thus, many issues regarding VSCs’s identity and function remain poorly understood. In fact, even after decades of intensive research, Mesenchymal Stem Cells (MSC), which is suggested to be VSCs, is still having many outstanding issues of its own. And, on top of this, likewise decades-long intensive pericyte research has not been able resolve the identity issue. While favors Adventitial Progenitor Cells (APCs) over pericytes as the likely VSC candidate, it should be pointed out that currently the opposite view (i.e., pericytes as VSCs) is more prevalent, and many excellent reviews, including a recent one, have discussed this issue extensively.SUMMARY: It has been postulated that, within the vasculature, APCs could differentiate into pericytes (CD34- CD31- CD140b+ SMA-), endothelial cells (CD34+ CD31+ CD140b- SMA-), and smooth muscle cells (SMCs) (CD34- CD31- CD140b- SMA+); and during tissue expansion or repair, APCs could also differentiate into tissue-specific cell types (e.g., muscle and fat) Thus, in vitro, APCs fulfill all criteria for being VSCs. Meanwhile, in vivo evidence is still limited and will require further investigation.KEYWORDS: vascular stem cells, VSC, mesenchymal stem cells, MSC, endothelial progenitor cells, EPC, adventitial progenitor cells, APC

scholarly journals In vivo cartilage-formation potency of somatic stem cells is associated with responsiveness to TGFβ stimulation in vitro

2021 ◽  
Author(s):  
Ryota Chijimatsu ◽  
Satoshi Miwa ◽  
Gensuke Okamura ◽  
Junya Miyahara ◽  
Naohiro Tachibana ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Transforming Growth Factor ◽  
Cartilage Regeneration ◽  
Cell Types ◽  
Transforming Growth Factor Β1 ◽  
Cartilage Defects ◽  
Chondrogenic Potential

Abstract Background: Somatic stem cell transplantation has been performed for cartilage injury, but the reparative mechanisms are still conflicting. The chondrogenic potential of stem cells are thought as promising features for cartilage therapy, however the correlation between their potential for chondrogenesis in vitro and in vivo remains undefined. The purpose of this study was to investigate the intrinsic chondrogenic condition depends on cell types and explore an indicator to select useful stem cells for cartilage regeneration.Methods: The chondrogenic potential of two different stem cell types derived from adipose tissue (ASCs) and synovium (SSCs) of mice and humans was assessed using bone morphogenic protein-2 (BMP2) and transforming growth factor-β1 (TGFβ1). Their reparative potential was also validated through transplantation into a mouse osteochondral defect model.Results: All cell types showed apparent chondrogenesis under the combination of BMP2 and TGFβ1 in vitro, as assessed by the formation of proteoglycan- and type 2 collagen (COL2)-rich tissues. However, our results vastly differed with those observed following single stimulation among species and cell types; apparent chondrogenesis of mouse ASCs, mouse SSCs, and human SSCs was observed with supplementation of BMP2, either BMP2 and TGFβ1, and BMP2, respectively. Human ASCs showed no chondrogenesis following single stimulation. Among human SSCs, two of six donors formed partially COL2-positive tissues in response to TGFβ1. However, unlike mouse cells, human cells showed fibrous components (COL1/3) with all treatments. Mouse SSCs formed hyaline-like cartilage (proteoglycan+/COL2+/COL1-/COL3-) in the transplanted site in vivo, but other cell types mainly formed COL1/3-positive fibrous tissues. Remarkably, only donors that showed chondrogenic response to TGFβ1 in vitro formed partially COL2-positive tissues in vivo. However, the area was mainly composed of COL1/3, indicating fibrous cartilage-like tissues.Conclusion: The chondrogenic response to TGFβ1 may represent the fate of stem cells when locally transplanted into cartilage defects.

scholarly journals Biomaterial Approaches for Stem Cell-Based Myocardial Tissue Engineering

2015 ◽  
Vol 10s1 ◽  
pp. BMI.S20313 ◽  
Author(s):  
Josh Cutts ◽  
Mehdi Nikkhah ◽  
David A. Brafman
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Raw Materials ◽  
Cell Types ◽  
Heart Tissue ◽  
Cardiac Damage ◽  
Low Efficiency

Adult and pluripotent stem cells represent a ready supply of cellular raw materials that can be used to generate the functionally mature cells needed to replace damaged or diseased heart tissue. However, the use of stem cells for cardiac regenerative therapies is limited by the low efficiency by which stem cells are differentiated in vitro to cardiac lineages as well as the inability to effectively deliver stem cells and their derivatives to regions of damaged myocardium. In this review, we discuss the various biomaterial-based approaches that are being implemented to direct stem cell fate both in vitro and in vivo. First, we discuss the stem cell types available for cardiac repair and the engineering of naturally and synthetically derived biomaterials to direct their in vitro differentiation to the cell types that comprise heart tissue. Next, we describe biomaterial-based approaches that are being implemented to enhance the in vivo integration and differentiation of stem cells delivered to areas of cardiac damage. Finally, we present emerging trends of using stem cell-based biomaterial approaches to deliver pro-survival factors and fully vascularized tissue to the damaged and diseased cardiac tissue.

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