scholarly journals Metabolomic Alteration of Oral Keratinocytes and Fibroblasts in Hypoxia

2021 ◽  
Vol 10 (6) ◽  
pp. 1156
Author(s):  
Hiroko Kato ◽  
Masahiro Sugimoto ◽  
Ayame Enomoto ◽  
Miku Kaneko ◽  
Yuko Hara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Oxygen Concentration ◽  
Culture Conditions ◽  
Metabolic Reprogramming ◽  
Metabolic Profiles ◽  
Quiescent State ◽  
Oral Keratinocytes ◽  
Somatic Stem Cells ◽  
Hypoxic Conditions

The oxygen concentration in normal human tissue under physiologic conditions is lower than the atmospheric oxygen concentration. The more hypoxic condition has been observed in the cells with wound healing and cancer. Somatic stem cells reside in a hypoxic microenvironment in vivo and prefer hypoxic culture conditions in vitro. Oral mucosa contains tissue-specific stem cells, which is an excellent tissue source for regenerative medicine. For clinical usage, maintaining the stem cell in cultured cells is important. We previously reported that hypoxic culture conditions maintained primary oral keratinocytes in an undifferentiated and quiescent state and enhanced their clonogenicity. However, the metabolic mechanism of these cells is unclear. Stem cell biological and pathological findings have shown that metabolic reprogramming is important in hypoxic culture conditions, but there has been no report on oral mucosal keratinocytes and fibroblasts. Herein, we conducted metabolomic analyses of oral mucosal keratinocytes and fibroblasts under hypoxic conditions. Hypoxic oral keratinocytes and fibroblasts showed a drastic change of metabolite concentrations in urea cycle metabolites and polyamine pathways. The changes of metabolic profiles in glycolysis and the pentose phosphate pathway under hypoxic conditions in the oral keratinocytes were consistent with those of other somatic stem cells. The metabolic profiles in oral fibroblasts showed only little changes in any pathway under hypoxia except for a significant increase in the antioxidant 2-oxoglutaric acid. This report firstly provides the holistic changes of various metabolic pathways of hypoxic cultured oral keratinocytes and fibroblasts.

scholarly journals Strategy to Establish Embryo-Derived Pluripotent Stem Cells in Cattle

2021 ◽  
Vol 22 (9) ◽  
pp. 5011
Author(s):  
Daehwan Kim ◽  
Sangho Roh
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Stem Cell Research ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Culture Conditions ◽  
Human Diseases ◽  
Induced Pluripotent

Stem cell research is essential not only for the research and treatment of human diseases, but also for the genetic preservation and improvement of animals. Since embryonic stem cells (ESCs) were established in mice, substantial efforts have been made to establish true ESCs in many species. Although various culture conditions were used to establish ESCs in cattle, the capturing of true bovine ESCs (bESCs) has not been achieved. In this review, the difficulty of establishing bESCs with various culture conditions is described, and the characteristics of proprietary induced pluripotent stem cells and extended pluripotent stem cells are introduced. We conclude with a suggestion of a strategy for establishing true bESCs.

scholarly journals Region-specific regulation of stem cell-driven regeneration in tapeworms

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Tania Rozario ◽  
Edward B Quinn ◽  
Jianbin Wang ◽  
Richard E Davis ◽  
Phillip A Newmark
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Rna Interference ◽  
Head And Neck ◽  
Hymenolepis Diminuta ◽  
Somatic Stem Cells ◽  
Extrinsic Cues ◽  
Specific Regulation

Tapeworms grow at rates rivaling the fastest-growing metazoan tissues. To propagate they shed large parts of their body; to replace these lost tissues they regenerate proglottids (segments) as part of normal homeostasis. Their remarkable growth and regeneration are fueled by adult somatic stem cells that have yet to be characterized molecularly. Using the rat intestinal tapeworm, Hymenolepis diminuta, we find that regenerative potential is regionally limited to the neck, where head-dependent extrinsic signals create a permissive microenvironment for stem cell-driven regeneration. Using transcriptomic analyses and RNA interference, we characterize and functionally validate regulators of tapeworm growth and regeneration. We find no evidence that stem cells are restricted to the regeneration-competent neck. Instead, lethally irradiated tapeworms can be rescued when cells from either regeneration-competent or regeneration-incompetent regions are transplanted into the neck. Together, the head and neck tissues provide extrinsic cues that regulate stem cells, enabling region-specific regeneration in this parasite.

scholarly journals Engineering large cartilage tissues using dynamic bioreactor culture at defined oxygen conditions

2018 ◽  
Vol 9 ◽  
pp. 204173141775371 ◽  
Author(s):  
Andrew C Daly ◽  
Binulal N Sathy ◽  
Daniel J Kelly
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Culture Conditions ◽  
Cartilage Tissue ◽  
Bioreactor Culture ◽  
Dynamic Culture ◽  
Oxygen Conditions ◽  
Static Conditions

Mesenchymal stem cells maintained in appropriate culture conditions are capable of producing robust cartilage tissue. However, gradients in nutrient availability that arise during three-dimensional culture can result in the development of spatially inhomogeneous cartilage tissues with core regions devoid of matrix. Previous attempts at developing dynamic culture systems to overcome these limitations have reported suppression of mesenchymal stem cell chondrogenesis compared to static conditions. We hypothesize that by modulating oxygen availability during bioreactor culture, it is possible to engineer cartilage tissues of scale. The objective of this study was to determine whether dynamic bioreactor culture, at defined oxygen conditions, could facilitate the development of large, spatially homogeneous cartilage tissues using mesenchymal stem cell laden hydrogels. A dynamic culture regime was directly compared to static conditions for its capacity to support chondrogenesis of mesenchymal stem cells in both small and large alginate hydrogels. The influence of external oxygen tension on the response to the dynamic culture conditions was explored by performing the experiment at 20% O2 and 3% O2. At 20% O2, dynamic culture significantly suppressed chondrogenesis in engineered tissues of all sizes. In contrast, at 3% O2 dynamic culture significantly enhanced the distribution and amount of cartilage matrix components (sulphated glycosaminoglycan and collagen II) in larger constructs compared to static conditions. Taken together, these results demonstrate that dynamic culture regimes that provide adequate nutrient availability and a low oxygen environment can be employed to engineer large homogeneous cartilage tissues. Such culture systems could facilitate the scaling up of cartilage tissue engineering strategies towards clinically relevant dimensions.

Lin28 Enhances Glucose Metabolism in Human Placental Mesenchymal Stem Cells during Hypoxia via the PI3K-Akt Pathway

2021 ◽  
Author(s):  
Xi Zhou ◽  
Junbo Li ◽  
Jin Wang ◽  
Huifang Yang ◽  
Jingzeng Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Glucose Metabolism ◽  
Ischemia Reperfusion ◽  
Stem Cell Differentiation ◽  
Akt Signaling ◽  
Akt Pathway ◽  
Western Blots ◽  
Hypoxic Conditions

Abstract Mesenchymal stem cells (MSCs) are widely used to treat and prevent liver ischemia–reperfusion injury (LIRI), which commonly occurs after liver surgery. Lin28 is an RNA-binding protein crucial for early embryonic development, stem cell differentiation/reprogramming, tumorigenesis, and metabolism. However, whether Lin28 can enhance metabolism in human placental MSCs (PMSCs) during hypoxia to improve the protective effect against LIRI remains unclear. First, a Lin28 overexpression construct was introduced into PMSCs; glucose metabolism, the expression of glucose metabolism - and PI3K-AKT pathway-related proteins, and the levels of microRNA Let-7 family members were examined using a glucose metabolism kit, western blots, and real-time quantitative PCR, respectively. Next, treatment with an AKT inhibitor was performed to understand the association of Lin28 with the PI3K-Akt pathway. Subsequently, AML12 cells were co-cultured with PMSCs to construct an in vitro model of PMSC protecting liver cells from hypoxia injury. Finally, C57BL/6J mice were used to establish a partial warm hepatic ischemia–reperfusion model in vivo. Lin28 increased the glycolysis capacity of PMSCs, allowing these cells to produce more energy under hypoxic conditions. Lin28 also activated PI3K-Akt signaling under hypoxic conditions, and AKT inhibition attenuated the effects of Lin28. In addition, Lin28 overexpression was found to protect cells against LIRI-induced liver damage, inflammation, and apoptosis and attenuate hypoxia-induced hepatocyte injury. Inconclusion, Lin28 enhances glucose metabolism under hypoxic conditions in PMSCs, thereby providing protective effects against LIRI via the activation of the PI3K-Akt signaling pathway. Our study first reported the application of gene-modified mesenchymal stem cell-based therapy in LIRI.

From fibroblasts and stem cells: implications for cell therapies and somatic cloning

2005 ◽  
Vol 17 (2) ◽  
pp. 125 ◽  
Author(s):  
Wilfried A. Kues ◽  
Joseph W. Carnwath ◽  
Heiner Niemann
Keyword(s):  
Stem Cells ◽  
Adult Stem Cells ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Embryonic Stem ◽  
Culture Conditions ◽  
Human Embryos ◽  
Somatic Stem Cells ◽  
Primary Fibroblast ◽  
Cell Therapies

Pluripotent embryonic stem cells (ESCs) from the inner cell mass of early murine and human embryos exhibit extensive self-renewal in culture and maintain their ability to differentiate into all cell lineages. These features make ESCs a suitable candidate for cell-replacement therapy. However, the use of early embryos has provoked considerable public debate based on ethical considerations. From this standpoint, stem cells derived from adult tissues are a more easily accepted alternative. Recent results suggest that adult stem cells have a broader range of potency than imagined initially. Although some claims have been called into question by the discovery that fusion between the stem cells and differentiated cells can occur spontaneously, in other cases somatic stem cells have been induced to commit to various lineages by the extra- or intracellular environment. Recent data from our laboratory suggest that changes in culture conditions can expand a subpopulation of cells with a pluripotent phenotype from primary fibroblast cultures. The present paper critically reviews recent data on the potency of somatic stem cells, methods to modify the potency of somatic cells and implications for cell-based therapies.

scholarly journals Isolation and Culture of Human Stem Cells from Apical Papilla under Low Oxygen Concentration Highlight Original Properties

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1485 ◽  
Author(s):  
Murielle Rémy ◽  
Francesca Ferraro ◽  
Pierre Le Salver ◽  
Sylvie Rey ◽  
Elisabeth Genot ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Oxygen Concentration ◽  
Ambient Air ◽  
Stem Cell Marker ◽  
Autophagic Flux ◽  
Integrin Subunit ◽  
Differentiation Potential ◽  
Apical Papilla ◽  
The Impact

Stem cells isolated from the apical papilla of wisdom teeth (SCAPs) are an attractive model for tissue repair due to their availability, high proliferation rate and potential to differentiate in vitro towards mesodermal and neurogenic lineages. Adult stem cells, such as SCAPs, develop in stem cell niches in which the oxygen concentration [O2] is low (3–8% compared with 21% of ambient air). In this work, we evaluate the impact of low [O2] on the physiology of SCAPs isolated and processed in parallel at 21% or 3% O2 without any hyperoxic shock in ambient air during the experiment performed at 3% O2. We demonstrate that SCAPs display a higher proliferation capacity at 3% O2 than in ambient air with elevated expression levels of two cell surface antigens: the alpha-6 integrin subunit (CD49f) and the embryonic stem cell marker (SSEA4). We show that the mesodermal differentiation potential of SCAPs is conserved at early passage in both [O2], but is partly lost at late passage and low [O2], conditions in which SCAPs proliferate efficiently without any sign of apoptosis. Unexpectedly, we show that autophagic flux is active in SCAPs irrespective of [O2] and that this process remains high in cells even after prolonged exposure to 3% O2.

scholarly journals Plasticity and Potency of Mammary Stem Cell Subsets During Mammary Gland Development

2019 ◽  
Vol 20 (9) ◽  
pp. 2357 ◽  
Author(s):  
Eunmi Lee ◽  
Raziye Piranlioglu ◽  
Max S. Wicha ◽  
Hasan Korkaya
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mammary Gland ◽  
Mammary Gland Development ◽  
Mammary Epithelial ◽  
Stem Cell Markers ◽  
Quiescent State ◽  
Mammary Stem Cells ◽  
Mammary Stem ◽  
Gland Development

It is now widely believed that mammary epithelial cell plasticity, an important physiological process during the stages of mammary gland development, is exploited by the malignant cells for their successful disease progression. Normal mammary epithelial cells are heterogeneous and organized in hierarchical fashion, in which the mammary stem cells (MaSC) lie at the apex with regenerative capacity as well as plasticity. Despite the fact that the majority of studies supported the existence of multipotent MaSCs giving rise to both basal and luminal lineages, others proposed lineage restricted unipotent MaSCs. Consistent with the notion, the latest research has suggested that although normal MaSC subsets mainly stay in a quiescent state, they differ in their reconstituting ability, spatial localization, and molecular and epigenetic signatures in response to physiological stimuli within the respective microenvironment during the stages of mammary gland development. In this review, we will focus on current research on the biology of normal mammary stem cells with an emphasis on properties of cellular plasticity, self-renewal and quiescence, as well as the role of the microenvironment in regulating these processes. This will include a discussion of normal breast stem cell heterogeneity, stem cell markers, and lineage tracing studies.

scholarly journals Alternative polyadenylation of Pax3 controls muscle stem cell fate and muscle function

Science ◽  
2019 ◽  
Vol 366 (6466) ◽  
pp. 734-738 ◽  
Author(s):  
Antoine de Morree ◽  
Julian D. D. Klein ◽  
Qiang Gan ◽  
Jean Farup ◽  
Andoni Urtasun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Messenger Rna ◽  
Adult Stem Cells ◽  
Alternative Polyadenylation ◽  
Quiescent State ◽  
Stem Cell Fate ◽  
Activation Rate

Adult stem cells are essential for tissue homeostasis. In skeletal muscle, muscle stem cells (MuSCs) reside in a quiescent state, but little is known about the mechanisms that control homeostatic turnover. Here we show that, in mice, the variation in MuSC activation rate among different muscles (for example, limb versus diaphragm muscles) is determined by the levels of the transcription factor Pax3. We further show that Pax3 levels are controlled by alternative polyadenylation of its transcript, which is regulated by the small nucleolar RNA U1. Isoforms of the Pax3 messenger RNA that differ in their 3′ untranslated regions are differentially susceptible to regulation by microRNA miR206, which results in varying levels of the Pax3 protein in vivo. These findings highlight a previously unrecognized mechanism of the homeostatic regulation of stem cell fate by multiple RNA species.

scholarly journals The Leukemic Stem Cell Niche: Adaptation to “Hypoxia” versus Oncogene Addiction

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Giulia Cheloni ◽  
Martina Poteti ◽  
Silvia Bono ◽  
Erico Masala ◽  
Nathalie M. Mazure ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Oxygen Concentration ◽  
Residual Disease ◽  
Adaptation To Hypoxia ◽  
Oncogene Addiction ◽  
Low Oxygen ◽  
Niche Adaptation ◽  
Cell Incubation ◽  
Oncogenic Protein

Previous studies based on low oxygen concentrations in the incubation atmosphere revealed that metabolic factors govern the maintenance of normal hematopoietic or leukemic stem cells (HSC and LSC). The physiological oxygen concentration in tissues ranges between 0.1 and 5.0%. Stem cell niches (SCN) are placed in tissue areas at the lower end of this range (“hypoxic” SCN), to which stem cells are metabolically adapted and where they are selectively hosted. The data reported here indicated that driver oncogenic proteins of several leukemias are suppressed following cell incubation at oxygen concentration compatible with SCN physiology. This suppression is likely to represent a key positive regulator of LSC survival and maintenance (self-renewal) within the SCN. On the other hand, LSC committed to differentiation, unable to stand suppression because of addiction to oncogenic signalling, would be unfit to home in SCN. The loss of oncogene addiction in SCN-adapted LSC has a consequence of crucial practical relevance: the refractoriness to inhibitors of the biological activity of oncogenic protein due to the lack of their molecular target. Thus, LSC hosted in SCN are suited to sustain the long-term maintenance of therapy-resistant minimal residual disease.

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