A Mini Review Focused on the Recent Applications of Graphene Oxide in Stem Cell Growth and Differentiation

Stem cells are undifferentiated cells that can give rise to any types of cells in our body. Hence, they have been utilized for various applications, such as drug testing and disease modeling. However, for the successful of those applications, the survival and differentiation of stem cells into specialized lineages should be well controlled. Growth factors and chemical agents are the most common signals to promote the proliferation and differentiation of stem cells. However, those approaches holds several drawbacks such as the negative side effects, degradation or denaturation, and expensive. To address such limitations, nanomaterials have been recently used as a better approach for controlling stem cells behaviors. Graphene oxide is the derivative of graphene, the first two-dimensional (2D) materials in the world. Recently, due to its extraordinary properties and great biological effects on stem cells, many scientists around the world have utilized graphene oxide to enhance the differentiation potential of stem cells. In this mini review, we highlight the key advances about the effects of graphene oxide on controlling stem cell growth and various types of stem cell differentiation. We also discuss the possible molecular mechanisms of graphene oxide in controlling stem cell growth and differentiation.

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A Mini Review Focused on the Recent Applications of Graphene Oxide in Stem Cell Growth and Differentiation

10.20944/preprints201809.0047.v1 ◽

2018 ◽

Author(s):

Alexander Halim ◽

Qing Luo ◽

Yang Ju ◽

Guanbin Song

Keyword(s):

Stem Cells ◽

Graphene Oxide ◽

Stem Cell ◽

Cell Growth ◽

Disease Modeling ◽

Biological Effects ◽

Stem Cell Differentiation ◽

Differentiation Potential ◽

The World ◽

Cell Growth And Differentiation

Stem cells are undifferentiated cells which can give rise to any types of cells in our body. Hence, they have been utilized for various applications such as drug testing and disease modeling. However, for the successful of those applications, the survival and differentiation of stem cells into specialized lineages should be well controlled. Growth factors and chemical agents are the most common signals to promote the proliferation and differentiation of stem cells. However, those approaches holds several drawbacks such as the negative side effects, degradation or denaturation, and expensive. To address such limitations, nanomaterials have been recently used as a better approach for controlling stem cells behaviors. Graphene oxide is the derivative of graphene, the first 2D materials in the world. Recently, due to its extraordinary properties and great biological effects on stem cells, many scientists around the world have utilized graphene oxide to enhance the differentiation potential of stem cells. In this mini review, we highlight the key advances about the effects of graphene oxide on controlling stem cell growth and various types of stem cell differentiation. We also discuss the possible molecular mechanisms of graphene oxide in controlling stem cell growth and differentiation.

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DYRK1A Negatively Regulates CDK5-SOX2 Pathway and Self-Renewal of Glioblastoma Stem Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22084011 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4011

Author(s):

Brianna Chen ◽

Dylan McCuaig-Walton ◽

Sean Tan ◽

Andrew P. Montgomery ◽

Bryan W. Day ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Differentiation ◽

Critical Role ◽

Stem Cell Differentiation ◽

Neural Progenitor Cell ◽

Cellular Heterogeneity ◽

Differentiation Potential ◽

Glioblastoma Stem Cells ◽

Glioblastoma Stem Cell

Glioblastoma display vast cellular heterogeneity, with glioblastoma stem cells (GSCs) at the apex. The critical role of GSCs in tumour growth and resistance to therapy highlights the need to delineate mechanisms that control stemness and differentiation potential of GSC. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) regulates neural progenitor cell differentiation, but its role in cancer stem cell differentiation is largely unknown. Herein, we demonstrate that DYRK1A kinase is crucial for the differentiation commitment of glioblastoma stem cells. DYRK1A inhibition insulates the self-renewing population of GSCs from potent differentiation-inducing signals. Mechanistically, we show that DYRK1A promotes differentiation and limits stemness acquisition via deactivation of CDK5, an unconventional kinase recently described as an oncogene. DYRK1A-dependent inactivation of CDK5 results in decreased expression of the stemness gene SOX2 and promotes the commitment of GSC to differentiate. Our investigations of the novel DYRK1A-CDK5-SOX2 pathway provide further insights into the mechanisms underlying glioblastoma stem cell maintenance.

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Comparison of the Proliferation and Differentiation Potential of Human Urine-, Placenta Decidua Basalis-, and Bone Marrow-Derived Stem Cells

Stem Cells International ◽

10.1155/2018/7131532 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Chengguang Wu ◽

Long Chen ◽

Yi-zhou Huang ◽

Yongcan Huang ◽

Ornella Parolini ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Stem Cell Differentiation ◽

Cell Types ◽

Stem Cell Marker ◽

Differentiation Potential ◽

Multipotent Stem Cells ◽

Decidua Basalis

Human multipotent stem cell-based therapies have shown remarkable potential in regenerative medicine and tissue engineering applications due to their abilities of self-renewal and differentiation into multiple adult cell types under appropriate conditions. Presently, human multipotent stem cells can be isolated from different sources, but variation among their basic biology can result in suboptimal selection of seed cells in preclinical and clinical research. Thus, the goal of this study was to compare the biological characteristics of multipotent stem cells isolated from human bone marrow, placental decidua basalis, and urine, respectively. First, we found that urine-derived stem cells (USCs) displayed different morphologies compared with other stem cell types. USCs and placenta decidua basalis-derived mesenchymal stem cells (PDB-MSCs) had superior proliferation ability in contrast to bone marrow-derived mesenchymal stem cells (BMSCs); these cells grew to have the highest colony-forming unit (CFU) counts. In phenotypic analysis using flow cytometry, similarity among all stem cell marker expression was found, excluding CD29 and CD105. Regarding stem cell differentiation capability, USCs were observed to have better adipogenic and endothelial abilities as well as vascularization potential compared to BMSCs and PDB-MSCs. As for osteogenic and chondrogenic induction, BMSCs were superior to all three stem cell types. Future therapeutic indications and clinical applications of BMSCs, PDB-MSCs, and USCs should be based on their characteristics, such as growth kinetics and differentiation capabilities.

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Epigenetics, Stem Cells, and Autophagy: Exploring a Path Involving miRNA

International Journal of Molecular Sciences ◽

10.3390/ijms20205091 ◽

2019 ◽

Vol 20 (20) ◽

pp. 5091 ◽

Cited By ~ 4

Author(s):

Francesca Balzano ◽

Ilaria Campesi ◽

Sara Cruciani ◽

Giuseppe Garroni ◽

Emanuela Bellu ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Dna Methyltransferase ◽

Main Tool ◽

Stem Cell Differentiation ◽

Differentiation Potential ◽

Multipotent Stem Cells ◽

Regulatory Circuit ◽

Stem Cell Pluripotency ◽

Males And Females

MiRNAs, a small family of non-coding RNA, are now emerging as regulators of stem cell pluripotency, differentiation, and autophagy, thus controlling stem cell behavior. Stem cells are undifferentiated elements capable to acquire specific phenotype under different kind of stimuli, being a main tool for regenerative medicine. Within this context, we have previously shown that stem cells isolated from Wharton jelly multipotent stem cells (WJ-MSCs) exhibit gender differences in the expression of the stemness related gene OCT4 and the epigenetic modulator gene DNA-Methyltransferase (DNMT1). Here, we further analyze this gender difference, evaluating adipogenic and osteogenic differentiation potential, autophagic process, and expression of miR-145, miR-148a, and miR-185 in WJ-MSCs derived from males and females. These miRNAs were selected since they are involved in OCT4 and DNMT1 gene expression, and in stem cell differentiation. Our results indicate a difference in the regulatory circuit involving miR-148a/DNMT1/OCT4 autophagy in male WJ-MSCs as compared to female cells. Moreover, no difference was detected in the expression of the two-differentiation regulating miRNA (miR-145 and miR-185). Taken together, our results highlight a different behavior of WJ-MSCs from males and females, disclosing the chance to better understand cellular processes as autophagy and stemness, usable for future clinical applications.

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The Influence of Metalized Graphene Oxide/Reduced Graphene Oxide and Sulfonated Polystyrene on Dental Pulp Stem Cell Differentiation and Protein Adsorption

MRS Advances ◽

10.1557/adv.2017.258 ◽

2017 ◽

Vol 2 (19-20) ◽

pp. 1059-1070 ◽

Cited By ~ 1

Author(s):

Rachel Sacks ◽

Gila Schein ◽

Rebecca Isseroff ◽

Vincent Ricotta ◽

Marcia Simon ◽

...

Keyword(s):

Graphene Oxide ◽

Stem Cell ◽

Protein Adsorption ◽

Dental Pulp ◽

Stem Cell Differentiation ◽

Sulfonated Polystyrene ◽

Reduced Graphene ◽

Human Dental Pulp ◽

Osteogenic Induction ◽

Cell Growth And Differentiation

ABSTRACTHuman dental pulp stem cells (DPSCs) can differentiate, showing potential for regenerative medicine. Designing artificial surfaces with properties appropriate for the initiation of extracellular matrix (ECM) adsorption and organization is a critical step in tissue engineering and can greatly impact protein adhesion. Sulfonated polystyrene (SPS), used as a scaffold for tissue development, stimulates protein adsorption due to the increased negative charge of sulfonate.Graphene and graphene oxide (GO) sheets enhance stem cell growth and differentiation because they are soft membranes with “high in-plane” stiffness and have the potential to be transferable and implantable platforms. This project functionalized GO and reduced GO (RGO) with gold or silver nanoparticles, mixing with SPS to investigate their combined impact on DPSC differentiation and protein adsorption, hypothesizing that this combination supplies more charges to better absorb the proteins to the surface and stimulate differentiation.Results indicate that proteins of cells plated on the gold-RGO/SPS surfaces were the most highly adsorbed and most densely packed. Additionally, the cell moduli data indicated that the metal-RGO solutions substantially induced a change in modulus even more than Dexamethasone, a glucocortoid known to enhance this process in DPSCs. This suggests that the metal-RGO solutions may be instrumental in osteogenic induction.

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Regulation of Hematopoietic Stem Cells by Interferons and by DNA Methylation: Implications for Bone Marrow Failure

Blood ◽

10.1182/blood.v124.21.sci-20.sci-20 ◽

2014 ◽

Vol 124 (21) ◽

pp. SCI-20-SCI-20

Author(s):

Margaret A. Goodell

Keyword(s):

Dna Methylation ◽

Stem Cells ◽

Bone Marrow ◽

Stem Cell ◽

Hematopoietic Stem Cells ◽

Bone Marrow Failure ◽

Stem Cell Differentiation ◽

Primary Myelofibrosis ◽

Differentiation Potential ◽

Hematopoietic Stem

Bone marrow failure (BMF), the inability to regenerate the differentiated cells of the blood, has a number of genetic and environmental etiologies, such as mutation of telomere-associated protein genes and immune-related aplastic anemia. Recently, mutations in DNA methyltransferase 3A (DNMT3A) have been found to be associated with approximately 15% of cases of primary myelofibrosis (MF), which can be a cause of BMF. The role of DNMT3A more broadly in hematopoiesis, and specifically in BMF, is currently poorly understood. DNMT3A is one of two de novo DNA methylation enzymes important in developmental fate choice. We showed that Dnmt3a is critical for normal murine hematopoiesis, as hematopoietic stem cells (HSCs) from Dnmt3a knockout (KO) mice displayed greatly diminished differentiation potential while their self-renewal ability was markedly increased1, in effect, leading to failure of blood regeneration or BMF. Combined with loss of Dnmt3b, HSCs exhibited a profound differentiation block, mediated in part by an increase of stabilized b-catenin. While we did not initially observe bone marrow pathology or malignancy development in mice transplanted with Dnmt3a KO HSCs, when we aged a large cohort of mice, all mice succumbed to hematologic disease within about 400 days. Roughly one-third of mice developed frank leukemia (acute lymphocytic leukemia or acute myeloid leukemia), one-third developed MDS, and the remainder developed primary myelofibrosis or chronic myelomonocytic leukemia. The pathological characteristics of the mice broadly mirror those of patients, suggesting the Dnmt3a KO mice can serve as a model for human DNMT3A-mutation associated disease. Strikingly, bone marrow of mice with different disease types exhibit distinct DNA methylation features. These will findings and the implications for disease development will be discussed. We are currently investigating the factors that drive different outcomes in the mice, including stressors such as exposure to interferons. We have hypothesized that HSC proliferation accelerates the Dnnmt3a-associated disease phenotypes. We have previously shown that interferons directly impinge on HSCs in the context of infections. Interferons activate HSCs to divide, generating differentiated progeny and cycling HSCs. Repeated interferon stimulation may permanently impair HSC function and bias stem cell output. When combined with loss of Dnmt3a, interferons may promote BMF. We will discuss broadly how external factors such as aging and infection may collaborate with specific genetic determinants to affect long-term hematopoiesis and malignancy development. Reference: Challen GA, Sun D, Jeong M, et al. Dnmt3a is essential for hematopoietic stem cell differentiation. Nat Genet 2012; 44: 23-31 Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Emerging Potential of Exosomes on Adipogenic Differentiation of Mesenchymal Stem Cells

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.649552 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yuxuan Zhong ◽

Xiang Li ◽

Fanglin Wang ◽

Shoushuai Wang ◽

Xiaohong Wang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Cell Differentiation ◽

Adipogenic Differentiation ◽

Stem Cell Differentiation ◽

Cartilage Tissue ◽

Differentiation Potential ◽

Engineering Research ◽

Adipose Tissue Engineering

The mesenchymal stem cells have multidirectional differentiation potential and can differentiate into adipocytes, osteoblasts, cartilage tissue, muscle cells and so on. The adipogenic differentiation of mesenchymal stem cells is of great significance for the construction of tissue-engineered fat and the treatment of soft tissue defects. Exosomes are nanoscale vesicles secreted by cells and widely exist in body fluids. They are mainly involved in cell communication processes and transferring cargo contents to recipient cells. In addition, exosomes can also promote tissue and organ regeneration. Recent studies have shown that various exosomes can influence the adipogenic differentiation of stem cells. In this review, the effects of exosomes on stem cell differentiation, especially on adipogenic differentiation, will be discussed, and the mechanisms and conclusions will be drawn. The main purpose of studying the role of these exosomes is to understand more comprehensively the influencing factors existing in the process of stem cell differentiation into adipocytes and provide a new idea in adipose tissue engineering research.

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Differentiation Hotspots on a Cell Cycle Related Continuum.

Blood ◽

10.1182/blood.v110.11.3703.3703 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3703-3703

Author(s):

Gerald A. Colvin ◽

David Berz ◽

Mark S. Dooner ◽

Gerri J. Dooner ◽

Kevin Johnson ◽

...

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Stem Cell ◽

Stem Cell Differentiation ◽

S Phase ◽

Differentiation Potential ◽

Steel Factor ◽

A Cell ◽

Inductive Signaling

Abstract Directed differentiation is defined as the ability to program a stem cell at the most primitive level while it still has its reproductive and full proliferative potential. This is in contrast to ex-vivo expansion where the stem cells are forced into specific lineage commitments, limiting the overall therapeutic utility. We have demonstrated differentiation “hotspots” on a cell cycle continuum (Exp Heme35:96, 2007). In this work we showed marked but reversible increases in differentiation potential to megakryocyte and granulocytes at different phases of a single cytokine induced cell cycle passage of highly purified quiescent murine lineagenegative rhodaminelowHoeschtlow (LRH) marrow stem cells. We have reproducibly induced directed stem cell differentiation by capitalizing on inherent changes in sensitivities to inductive cytokine signals in the context of cell cycle position. These cells, when exposed to thrombopoietin, FLT3-ligand and steel factor, synchronously pass through cell cycle. We have found that using a differentiation cytokine cocktail of G-CSF at 0.075ng/ml, GM-CSF at 0.0375ng/ml and steel factor at 50ng/ml, we were able to see enhanced megakaryopoiesis occurring 14-days after culture in those LRH stem cells that were in early to mid S-phase at time of inductive signaling. We have now shown that a megakaryocyte hotspot clusters around 32 hours; the G1/S interface, and that dramatic reversible changes in differentiation potential occur over one hour time intervals. We have confirmed this data by looking at LRH cells through cell cycle transit after initial cell division showing that a megakaryocyte hotspot occurs in two sequential cell cycles and still tied to S-phase at time of inductive signaling of the daughter cells. This hotspot has been demonstrated on a clonal basis, although the kinetics of the hotspot shifts when clonal as opposed to population studies are carried out. An important issue is whether in vitro cytokine exposure, separate from cell cycle status, determines the existence of the hotspot. To address this, we used Hoechst 33342 dye content to assist in separation of different cell cycle fractions (G0–1, early, mid and late components of S, G2/M) of lineage negative Sca-1+ stem cells, a cycling stem/progenitor cell population in which approximately 20% of the cells are in S-phase at isolation. These cells were only exposed to the differentiation cytokines and showed a megakaryocyte hotspot present in only early S-phase cells after 14-days of culture, showing that in vitro cell cycle phase determined the presence of the hotspot, separate from cytokine exposure. These data indicate that differentiation potential of marrow stem cells exists on a cell cycle related continuum and that this potential can be demonstrated on a single cell basis. This suggests a continuum model of stem cell regulation at the stem cell level as opposed to a pure hierarchical model.

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Graphene Oxide: A Promising Material for Regenerative Medicine and Tissue Engineering

BioMolecular Concepts ◽

10.1515/bmc-2020-0017 ◽

2020 ◽

Vol 11 (1) ◽

pp. 182-200

Author(s):

Masomeh Maleki ◽

Reza Zarezadeh ◽

Mohammad Nouri ◽

Aydin Raei Sadigh ◽

Farhad Pouremamali ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Graphene Oxide ◽

Stem Cell ◽

Regenerative Medicine ◽

Stem Cell Differentiation ◽

Body Parts ◽

Great Opportunity ◽

Differentiation And Proliferation

AbstractRegenerative medicine and tissue engineering have been considered pioneer fields in the life sciences, with an ultimate goal of restoring or switching lost or impaired body parts. Graphene oxide (GO) is the product of graphene oxidation and presents a great opportunity to make substantial progress in the field of regenerative medicine; for example, it supports the possibility of creating a cellular niche for stem cells on a nanoparticle surface. GO creates a fascinating structure for regulating stem cell behavior, as it can potentially applied to the noninvasive chase of stem cells in vivo, the liberation of active biological factors from stem cell-containing delivery systems, and the intracellular delivery of factors such as growth factors, DNA, or synthetic proteins in order to modulate stem cell differentiation and proliferation. Due to the interesting physicochemical properties of GO and its possible usage in tissue engineering approaches, the present review aims to elaborate on the ways in which GO can improve current regenerative strategies. In this respect, the applicability of GO to the repair and regeneration of various tissues and organs, including cardiac muscle, skeletal muscle, and nervous, bone, cartilage, adipose, and skin tissues, is discussed.

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