Nanomaterials and Stem Cell Differentiation Potential: An Overview of Biological Aspects and Biomedical Efficacy

: Nanoparticles (NPs) due to their medical applications are widely used. Accordingly, the use of mesenchymal stem cells is one of the most important alternatives in tissue engineering field. NPs play effective roles in stem cells proliferation and differentiation. The combination of NPs and tissue regeneration by stem cells has created new therapeutic approach towards humanity. Of note, the physicochemical properties of NPs determine their biological function. Interestingly, various mechanisms such as modulation of signaling pathways and generation of reactive oxygen species, are involved in NPs-induced cellular proliferation and differentiation. This review summarized the types of nanomaterials effective on stem cell differentiation, the physicochemical features, biomedical application of these materials and relationship between nanomaterials and environment.

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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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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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Mitochondria regulate Drosophila intestinal stem cell differentiation through FOXO

10.1101/2020.02.12.946194 ◽

2020 ◽

Author(s):

Fan Zhang ◽

Mehdi Pirooznia ◽

Hong Xu

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Differentiation ◽

Stem Cell Differentiation ◽

Common Belief ◽

Atp Production ◽

Transport Chain ◽

Ros Accumulation ◽

Proliferation And Differentiation

AbstractStem cells often rely on glycolysis for energy production, and switching to oxidative phosphorylation is believed to be essential for their differentiation. To explore the link between mitochondrial respiration and stem cell differentiation, we genetically disrupted electron transport chain (ETC) complexes in the intestinal stem cells (ISCs) of Drosophila. We found that ISCs carrying impaired ETC proliferated much more slowly than normal, produced very few intestinal progenitors, or enteroblasts, and failed to differentiate into enterocytes or enteroendocrine cells. One of the main impediments to ISCs’ differentiation appeared to be abnormally elevated forkhead box O (FOXO) signaling in the ETC-deficient ISCs, as genetically suppressing the signaling pathway partially rescued the differentiation defect. Contrary to common belief, neither reactive oxygen species (ROS) accumulation nor adenosine triphosphate (ATP) reduction appeared to mediate the ETC mutant phenotype. Our results demonstrate that ETC is essential for Drosophila ISC proliferation and differentiation in vivo, and acts at least partially by repressing endogenous FOXO signaling. They also raise the possibility that ETC complexes have a role in stem cell differentiation beyond electron transfer and ATP production.

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Recognition of tenogenic differentiation using convolutional neural network

Current Directions in Biomedical Engineering ◽

10.1515/cdbme-2020-3051 ◽

2020 ◽

Vol 6 (3) ◽

pp. 200-204

Author(s):

Gözde Dursun ◽

Saurabh Balkrishna Tandale ◽

Jörg Eschweiler ◽

Mersedeh Tohidnezhad ◽

Bernd Markert ◽

...

Keyword(s):

Neural Networks ◽

Stem Cells ◽

Stem Cell ◽

Cell Differentiation ◽

High Performance ◽

Image Data ◽

Stem Cell Differentiation ◽

Differentiation Potential ◽

Non Invasive ◽

Invasive Cell

AbstractMethodologies to assess stem cell differentiation in the culturing state are needed for regenerative medicine and tissue engineering techniques. In recent years, convolutional neural networks (CNNs), a class of deep neural networks, have made impressive advancements in image-based classification, recognition and detection tasks. CNNs have been introduced as a non-invasive cell characterization method by learning features directly from image data of unlabeled cells. Furthermore, this approach serves as a rapid and inexpensive methodology with high performance compared to traditional techniques that require complex laboratory procedures including antibody staining and gene expression analysis. Here, we studied the potential of the CNNs approach to recognize stem cell differentiation based on cell morphology utilizing phasecontrast microscopy images.We have examined the differentiation potential of bone marrow mesenchymal stem cells (BMSCs) into tenocytes, with the treatment of bone morphogenetic protein-12 (BMP-12). After treatment, the phase-contrast images of cells were obtained directly from cell culture flasks to train CNN and the differentiated phenotype of stem cells was characterized by immunostaining. CNN was able to classify the cells into three groups including non-stem cells (chondrocytes), stem cells (BMSCs) and differentiated stem cells (tenocytes) based on their morphology with 92.2 % accuracy. The presented study revealed that CNN performed faster and non-invasive cell classification task compared to traditional methodologies.

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Tendon-Derived Stem Cell Differentiation in the Degenerative Tendon Microenvironment

Stem Cells International ◽

10.1155/2018/2613821 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Chang Liu ◽

Jing-wan Luo ◽

Ke-ke Zhang ◽

Long-xiang Lin ◽

Ting Liang ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Differentiation ◽

Western Blot ◽

Real Time ◽

Cell Morphology ◽

Real Time Pcr ◽

Stem Cell Differentiation ◽

Proliferation And Differentiation ◽

Morphology Changes

Tendinopathy is prevalent in athletic and many occupational populations; nevertheless, the pathogenesis of tendinopathy remains unclear. Tendon-derived stem cells (TDSCs) were regarded as the key culprit for the development of tendinopathy. However, it is uncertain how TDSCs differentiate into adipocytes, chondrocytes, or osteocytes in the degenerative microenvironment of tendinopathy. So in this study, the regulating effects of the degenerative tendon microenvironment on differentiation of TDSCs were investigated. TDSCs were isolated from rat Achilles tendons and were grown on normal and degenerative (prepared by stress-deprived culture) decellularized tendon slices (DTSs). Immunofluorescence staining, H&E staining, real-time PCR, and Western blot were used to delineate the morphology, proliferation, and differentiation of TDSCs in the degenerative microenvironment. It was found that TDSCs were much more spread on the degenerative DTSs than those on normal DTSs. The tenocyte-related markers, COL1 and TNMD, were highly expressed on normal DTSs than the degenerative DTSs. The expression of chondrogenic and osteogenic markers, COL2, SOX9, Runx2, and ALP, was higher on the degenerative DTSs compared with TDSCs on normal DTSs. Furthermore, phosphorylated FAK and ERK1/2 were reduced on degenerative DTSs. In conclusion, this study found that the degenerative tendon microenvironment induced TDSCs to differentiate into chondrogenic and osteogenic lineages. It could be attributed to the cell morphology changes and reduced FAK and ERK1/2 activation in the degenerative microenvironment of tendinopathy.

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Regulation of Stem Cell Differentiation by Inorganic Nanomaterials: Recent Advances in Regenerative Medicine

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.721581 ◽

2021 ◽

Vol 9 ◽

Author(s):

Fumei He ◽

Jinxiu Cao ◽

Junyang Qi ◽

Zeqi Liu ◽

Gan Liu ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Differentiation ◽

Chemical Properties ◽

Stem Cell Differentiation ◽

Recent Advances ◽

Proliferation And Differentiation ◽

Inorganic Nanomaterials ◽

Physical And Chemical ◽

And Chemical Properties

Transplanting stem cells with the abilities of self-renewal and differentiation is one of the most effective ways to treat many diseases. In order to optimize the therapeutic effect of stem cell transplantation, it is necessary to intervene in stem cell differentiation. Inorganic nanomaterials (NMs), due to their unique physical and chemical properties, can affect the adhesion, migration, proliferation and differentiation of stem cells. In addition, inorganic NMs have huge specific surface area and modifiability that can be used as vectors to transport plasmids, proteins or small molecules to further interfere with the fate of stem cells. In this mini review, we summarized the recent advances of common inorganic NMs in regulating stem cells differentiation, and the effects of the stiffness, size and shape of inorganic NMs on stem cell behavior were discussed. In addition, we further analyzed the existing obstacles and corresponding perspectives of the application of inorganic NMs in the field of stem cells.

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Identification of cardiac stem cells with FLK1, CD31, and VE‐cadherin expression during embryonic stem cell differentiation

The FASEB Journal ◽

10.1096/fj.04-1998com ◽

2005 ◽

Vol 19 (3) ◽

pp. 371-378 ◽

Cited By ~ 38

Author(s):

Midori Iida ◽

Toshio Heike ◽

Momoko Yoshimoto ◽

Shiro Baba ◽

Hiraku Doi ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Differentiation ◽

Embryonic Stem Cell ◽

Embryonic Stem ◽

Stem Cell Differentiation ◽

Embryonic Stem Cell Differentiation ◽

Cardiac Stem Cells

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Nuclear Export of Smads by RanBP3L Regulates Bone Morphogenetic Protein Signaling and Mesenchymal Stem Cell Differentiation

Molecular and Cellular Biology ◽

10.1128/mcb.00121-15 ◽

2015 ◽

Vol 35 (10) ◽

pp. 1700-1711 ◽

Cited By ~ 15

Author(s):

Fenfang Chen ◽

Xia Lin ◽

Pinglong Xu ◽

Zhengmao Zhang ◽

Yanzhen Chen ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Cell Differentiation ◽

Mesenchymal Stem Cell ◽

Nuclear Export ◽

Stem Cell Differentiation ◽

Bmp Signaling ◽

Dependent Manner ◽

Mesenchymal Stem Cell Differentiation

Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance and differentiation. BMPs can induce osteogenesis and inhibit myogenesis of mesenchymal stem cells. Canonical BMP signaling is stringently controlled through reversible phosphorylation and nucleocytoplasmic shuttling of Smad1, Smad5, and Smad8 (Smad1/5/8). However, how the nuclear export of Smad1/5/8 is regulated remains unclear. Here we report that the Ran-binding protein RanBP3L acts as a nuclear export factor for Smad1/5/8. RanBP3L directly recognizes dephosphorylated Smad1/5/8 and mediates their nuclear export in a Ran-dependent manner. Increased expression of RanBP3L blocks BMP-induced osteogenesis of mouse bone marrow-derived mesenchymal stem cells and promotes myogenic induction of C2C12 mouse myoblasts, whereas depletion of RanBP3L expression enhances BMP-dependent stem cell differentiation activity and transcriptional responses. In conclusion, our results demonstrate that RanBP3L, as a nuclear exporter for BMP-specific Smads, plays a critical role in terminating BMP signaling and regulating mesenchymal stem cell differentiation.

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