scholarly journals The Hypoxia-Mimetic Agent Cobalt Chloride Differently Affects Human Mesenchymal Stem Cells in Their Chondrogenic Potential

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Gabriella Teti ◽  
Stefano Focaroli ◽  
Viviana Salvatore ◽  
Eleonora Mazzotti ◽  
Laura Ingra’ ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Viability ◽  
Adult Stem Cells ◽  
Cobalt Chloride ◽  
Human Mscs ◽  
Low Oxygen ◽  
M Cell ◽  
Chondrogenic Potential

Adult stem cells are a promising cell source for cartilage regeneration. They resided in a special microenvironment known as the stem-cell niche, characterized by the presence of low oxygen concentration. Cobalt chloride (CoCl2) imitates hypoxia in vitro by stabilizing hypoxia-inducible factor-alpha (HIF-1α), which is the master regulator in the cellular adaptive response to hypoxia. In this study, the influence of CoCl2 on the chondrogenic potential of human MSCs, isolated from dental pulp, umbilical cord, and adipose tissue, was investigated. Cells were treated with concentrations of CoCl2 ranging from 50 to 400 μM. Cell viability, HIF-1α protein synthesis, and the expression of the chondrogenic markers were analyzed. The results showed that the CoCl2 supplementation had no effect on cell viability, while the upregulation of chondrogenic markers such as SOX9, COL2A1, VCAN, and ACAN was dependent on the cellular source. This study shows that hypoxia, induced by CoCl2 treatment, can differently influence the behavior of MSCs, isolated from different sources, in their chondrogenic potential. These findings should be taken into consideration in the treatment of cartilage repair and regeneration based on stem cell therapies.

Stem Cells from Human Exfoliated Deciduous Teeth: A Growing Literature

2016 ◽  
Vol 202 (5-6) ◽  
pp. 269-280 ◽  
Author(s):  
Daniel Martinez Saez ◽  
Robson Tetsuo Sasaki ◽  
Adriana da Costa Neves ◽  
Marcelo Cavenaghi Pereira da Silva
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Current Knowledge ◽  
Deciduous Teeth ◽  
Easy Access ◽  
Stem Cell Population ◽  
Scientific Publications ◽  
Human Exfoliated Deciduous Teeth

Adult stem cells research has been considered the most advanced sort of medical-scientific research, particularly stem cells from human exfoliated deciduous teeth (SHED), which represent an immature stem cell population. The purpose of this review is to describe the current knowledge concerning SHED from full-text scientific publications from 2003 to 2015, available in English language and based on the keyword and/or abbreviations ‘stem cells from human exfoliated deciduous teeth (SHED)', and individually presented as to the properties of SHED, immunomodulatory properties of SHED and stem cell banking. In summary, these cell populations are easily accessible by noninvasive procedures and can be isolated, cultured and expanded in vitro, successfully differentiated in vitro and in vivo into odontoblasts, osteoblasts, chondrocytes, adipocytes and neural cells, and present low immune reactions or rejection following SHED transplantation. Furthermore, SHED are able to remain undifferentiated and stable after long-term cryopreservation. In conclusion, the high proliferative capacity, easy access, multilineage differentiation capacity, noninvasiveness and few ethical concerns make stem cells from human exfoliated deciduous teeth the most valuable source of stem cells for tissue engineering and cell-based regenerative medicine therapies.

scholarly journals Advances and Applications in Stem Cell Biology

2012 ◽  
Vol 46 (2) ◽  
pp. 75-80
Author(s):  
Shamoli Bhattacharyya
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Adult Stem Cells ◽  
Great Promise ◽  
Stem Cell Biology ◽  
Self Renewal ◽  
Main Challenge ◽  
Basic Biology

ABSTRACT Mesenchymal stem cells have shown great promise as the source of adult stem cells for regenerative medicine. Present research efforts are directed at isolating these cells from various sources, growing them in vitro and maintaining their pluripotency as well as capacity for self renewal. It is crucial to identify the regulatory molecules which directly or indirectly control the proliferative status or influence the niche microenvironment. The main challenge is to understand the basic biology of the stem cells and manipulate them for further therapeutic applications. Considering their malignant potential, stem cells may be a double edged sword. While the benefits of these cells need to be harnessed judiciously, a significant amount of research is required before embarking on widespread use of this tool for the benefit of humanity. How to cite this article Bhattacharyya S. Advances and Applications in Stem Cell Biology. J Postgrad Med Edu Res 2012;46(2):75-80.

Abstract 213: Evolving Challenges in Promoting Stem Cell Based Cardiovascular Repair and Regeneration

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Mani T Valarmathi ◽  
Jiang Li
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cardiac Muscle ◽  
Adult Stem Cells ◽  
Cardiac Tissue ◽  
Three Dimensional ◽  
Induced Pluripotent Stem Cell ◽  
Myocardial Damage ◽  
Culture Conditions

Introduction: Use of adult stem cells in the stimulation of mammalian cardiac muscle regeneration is in its infancy, and to date, it has been difficult to determine the efficacy of the procedures that have been employed. The outstanding question remains whether stem cells derived from the bone-marrow or some other location within or outside of the heart can populate a region of myocardial damage and transform into tissue-specific cells, and also exhibit functional synchronization. As a result, this necessitates the development of an appropriate in vitro three-dimensional (3-D) model of cardiomyogenesis and prompts the development of a 3-D cardiac muscle construct for tissue engineering purposes, especially using the adult stem cells. Hypothesis: Functioning vascularized cardiac tissue can be generated by the interaction of human induced pluripotent stem cell-derived embryonic cardiac myocytes (hiPSC-ECMs) and human multipotent mesenchymal stem cells (hMSCs) on a 3-D prevascularized collagen cell carrier (CCC) scaffold. Methods and Results: In order to achieve the above aim, we have developed an in vitro 3-D functioning vascularized cardiac muscle construct using hiPSC-ECMs and hMSCs. First, to generate the prevascularized scaffold, human cardiac microvascular endothelial cells (hCMVECs) and hMSCs were co-cultured on 3-D CCCs for 7 days under vasculogenic culture conditions, hCMVECs/hMSCs underwent maturation, differentiation, and morphogenesis characteristic of micro vessels, and formed extensive plexuses of vascular networks. Next, the hiPSC-ECMs and hMSCs were co-cultured onto this generated prevascularized CCCs for further 7 or 14 days in myogenic culture conditions. Finally, the vascular and cardiac phenotypic inductions were analyzed at the morphological, immunological, biochemical, molecular, and functional levels. Expression and functional analyses of the differentiated cells revealed dramatic neo-angiogenesis and neo-cardiomyogenesis. Conclusions: Thus, our unique 3-D co-culture system provided us the apt in vitro functioning prevascularized 3-D cardiac patch that can be utilized for cellular cardiomyoplasty.

scholarly journals Chemical Genetic Screen in Drosophila Germline Uncovers Small Molecule Drugs That Sensitize Stem Cells to Insult-Induced Apoptosis

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2771
Author(s):  
Julien Roy Ishibashi ◽  
Riya Keshri ◽  
Tommy Henry Taslim ◽  
Daniel Kennedy Brewer ◽  
Tung Ching Chan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Small Molecule ◽  
Adult Stem Cells ◽  
Genetic Interactions ◽  
Germline Stem Cells ◽  
Drug Candidates ◽  
Chemical Genetic

Cancer stem cells, in contrast to their more differentiated daughter cells, can endure genotoxic insults, escape apoptosis, and cause tumor recurrence. Understanding how normal adult stem cells survive and go to quiescence may help identify druggable pathways that cancer stem cells have co-opted. In this study, we utilize a genetically tractable model for stem cell survival in the Drosophila gonad to screen drug candidates and probe chemical-genetic interactions. Our study employs three levels of small molecule screening: (1) a medium-throughput primary screen in male germline stem cells (GSCs), (2) a secondary screen with irradiation and protein-constrained food in female GSCs, and (3) a tertiary screen in breast cancer organoids in vitro. Herein, we uncover a series of small molecule drug candidates that may sensitize cancer stem cells to apoptosis. Further, we have assessed these small molecules for chemical-genetic interactions in the germline and identified the NF-κB pathway as an essential and druggable pathway in GSC quiescence and viability. Our study demonstrates the power of the Drosophila stem cell niche as a model system for targeted drug discovery.

Abstract 17305: The ER Unfolded Protein Response Effector, ATF6, Promotes Proliferation and Maintains Pluripotency in Cardiac Stem Cells

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Winston T Stauffer ◽  
Shirin Doroudgar ◽  
Haley N Stephens ◽  
Erik A Blackwood ◽  
Christopher C Glembotski
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Viability ◽  
Unfolded Protein Response ◽  
Cardiac Stem Cells ◽  
Antioxidant Gene ◽  
Unfolded Protein ◽  
Proliferation And Differentiation ◽  
Protein Response

Recent studies have suggested that multipotent stem cells residing in the adult heart, called cardiac stem cells (CSCs), mitigate damage in the infarcted or failing heart. Investigating the factors governing CSC proliferation and differentiation is key to understanding what role these cells play in the heart and in future therapeutic strategies. Additionally, activating transcription factor 6 (ATF6), an effector of the endoplasmic reticulum (ER) unfolded protein response (UPR), plays critical roles in development, as well as in the differentiation of certain stem cell types, though it has not been studied in this regard in the heart. Our lab has demonstrated that ATF6 in cardiac myocytes is cardioprotective in vivo during ischemia/reperfusion partly by virtue of its ability to induce an antioxidant gene program that reduces damaging reactive oxygen species (ROS). However, ATF6, and its involvement in antioxidant gene induction, have not been studied in CSCs. Therefore, here we hypothesized that activation of the ATF6 branch of the UPR in CSCs is important for their proliferation and differentiation, given that ROS is known to be essential for these processes. To address this hypothesis, we subjected cultured mouse CSCs to simulated ischemia and observed increased ATF6 target gene mRNA levels. This demonstrates that, despite their undifferentiated status, CSCs have a functional UPR, which can be activated in response to ischemic stress. ATF6 loss of function (LOF) in CSCs, via RNAi or chemical inhibitor, yielded a basal decrease in cell viability and an increase in several differentiation markers, similar to the effect of dexamethasone differentiation stimulus. Increased ROS was also observed in an ATF6 LOF model. Strikingly, cotreatment with a chemical ROS inhibitor significantly rescued cell viability and reduced markers of differentiation in CSCs with reduced ATF6 function. These results suggest that CSCs require a basal level of ATF6 activity to maintain their proliferation and pluripotentcy in vitro and that this is mediated by the role of ATF6 in the mitigation of ROS. This is an important finding given that stem cell expansion in vitro is a critical step in the characterization of stem cells and their use in many therapeutic treatment strategies.

scholarly journals Amniotic Fluid and Amniotic Membrane Stem Cells: Marker Discovery

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Maria G. Roubelakis ◽  
Ourania Trohatou ◽  
Nicholas P. Anagnou
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Amniotic Fluid ◽  
Amniotic Membrane ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
Stem Cell Population ◽  
Marker Discovery

Amniotic fluid (AF) and amniotic membrane (AM) have been recently characterized as promising sources of stem or progenitor cells. Both not only contain subpopulations with stem cell characteristics resembling to adult stem cells, such as mesenchymal stem cells, but also exhibit some embryonic stem cell properties like (i) expression of pluripotency markers, (ii) high expansion in vitro, or (iii) multilineage differentiation capacity. Recent efforts have been focused on the isolation and the detailed characterization of these stem cell types. However, variations in their phenotype, their heterogeneity described by different groups, and the absence of a single marker expressed only in these cells may prevent the isolation of a pure homogeneous stem cell population from these sources and their potential use of these cells in therapeutic applications. In this paper, we aim to summarize the recent progress in marker discovery for stem cells derived from fetal sources such as AF and AM, using novel methodologies based on transcriptomics, proteomics, or secretome analyses.

scholarly journals Defining Optimized Properties of Modified mRNA to Enhance Virus- and DNA- Independent Protein Expression in Adult Stem Cells and Fibroblasts

2015 ◽  
Vol 35 (4) ◽  
pp. 1360-1371 ◽  
Author(s):  
Frauke Hausburg ◽  
Silke Na ◽  
Natalia Voronina ◽  
Anna Skorska ◽  
Paula Müller ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Protein Expression ◽  
Cell Viability ◽  
Adult Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Cell Types ◽  
Cell Reprogramming ◽  
Different Origins

Background: By far, most strategies for cell reprogramming and gene therapy are based on the introduction of DNA after viral delivery. To avoid the high risks accompanying these goals, non-viral and DNA-free delivery methods for various cell types are required. Methods: Relying on an initially established PCR-based protocol for convenient template DNA production, we synthesized five differently modified EGFP mRNA (mmRNA) species, incorporating various degrees of 5-methylcytidine-5'-triphosphate (5mC) and pseudouridine-5'-triphosphate (Ψ). We then investigated their effect on i) protein expression efficiencies and ii) cell viability for human mesenchymal stem cells (hMSCs) and fibroblasts from different origins. Results: Our protocol allows highly efficient mmRNA production in vitro, enabling rapid and stable protein expression after cell transfection. However, our results also demonstrate that the terminally optimal modification needs to be defined in pilot experiments for each particular cell type. Transferring our approach to the conversion of fibroblasts into skeletal myoblasts using mmRNA encoding MyoD, we confirm the huge potential of mmRNA based protein expression for virus- and DNA-free reprogramming strategies. Conclusion: The achieved high protein expression levels combined with good cell viability not only in fibroblasts but also in hMSCs provides a promising option for mmRNA based modification of various cell types including slowly proliferating adult stem cells. Therefore, we are confident that our findings will substantially contribute to the improvement of efficient cell reprogramming and gene therapy approaches.

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 STEM CELLS NEWS UPDATE: A PERSONAL PERSPECTIVE

2013 ◽  
Vol 16 (2) ◽  
pp. 7-15 ◽  
Author(s):  
Shiu C. Wong
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Government Regulation ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Personal Perspective ◽  
Cryo Preservation

ABSTRACT This article is a follow-up to a previous Commentary published in 2011. It updates some of the events mentioned in that Commentary and continues with more interesting and exciting news on stem cell research and the emerging field of Regenerative Medicine. Some of the news includes: 1) the 2012 Nobel Prize for Medicine awarded to John B. Gurdon and Shinya Yamanaka; 2) the cloning of human embryonic stem cells; 3) the continued search for truly pluripotent adult stem cells via in vitro and in vivo protocols; 4) the breakthrough in organ replacements; 5) the global stem cell race; 6) the global stem cell cryo-preservation business; 7) the worldwide stem cell donor registries, and 8) the issue of government regulation on stem cell therapy

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