scholarly journals Nanosecond Pulsed Electric Fields Enhance Mesenchymal Stem Cells Differentiation via DNMT1 regulated OCT4/NANOG gene expression

2020 ◽  
Author(s):  
Kejia Li ◽  
Tong Ning ◽  
Hao Wang ◽  
Yangzi Jiang ◽  
Jue Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Electric Fields ◽  
Dna Methyltransferase ◽  
Fundamental Property ◽  
Pulsed Electric Fields ◽  
Differentiation Potential ◽  
Trilineage Differentiation ◽  
Nanosecond Pulsed Electric Fields ◽  
Pluripotency Genes

Abstract Background: Multiple strategies have been proposed to promote the differentiation potential of MSCs, which is the fundamental property in tissue formation and regeneration. However, these strategies are relatively inefficient that limit the application, thus more advanced methods are needed. In this study, we report a novel and efficient strategy, nanosecond pulsed electric fields (nsPEFs) stimulation, which can enhance the trilineage differentiation potential of MSCs; and further explained the mechanism behind. Methods: We used histological staining to screen out the nsPEFs parameters that promoted the trilineage differentiation potential of MSCs, and further proved the effect of nsPEFs by detecting the functional gene. In order to explore the corresponding mechanism, we examined the expression of pluripotency genes and the methylation of their promoters. Finally, we targeted the DNA methyltransferase which was affected by nsPEFs. Results: The trilineage differentiation of bone marrow derived MSCs was significantly enhanced in vitro by simply pre-treated with 5 pulses of nsPEFs stimulation (energy levels as 10 ns, 20 kV/cm; 100 ns, 10 kV/cm), and this was due to the nsPEFs demethylated the promoters of stem cell pluripotency genes OCT4 and NANOG through instantaneous downregulation of DNA Methylation Transferase 1 (DNMT1), thereby increased the expression of OCT4 and NANOG for up to 3 days, and created a treatment window period of stem cells. Conclusions: In summary, nsPEFs can enhance MSCs differentiation via the epigenetic regulation, and could be a safe and effective strategy for future stem cell application.

scholarly journals Nanosecond Pulsed Electric Fields Enhance Mesenchymal Stem Cells Differentiation via DNMT1 regulated OCT4/NANOG gene expression

2020 ◽  
Author(s):  
Kejia Li ◽  
Tong Ning ◽  
Hao Wang ◽  
Yangzi Jiang ◽  
Jue Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Electric Fields ◽  
Methylation Status ◽  
Pulsed Electric Fields ◽  
Differentiation Potential ◽  
Trilineage Differentiation ◽  
Nanosecond Pulsed Electric Fields ◽  
Pluripotency Genes

Abstract Background: Multiple strategies have been proposed to promote the differentiation potential of mesenchymal stem cells (MSCs), which is the fundamental property in tissue formation and regeneration. However, these strategies are relatively inefficient that limit the application. In this study, we reported a novel and efficient strategy, nanosecond pulsed electric fields (nsPEFs) stimulation, which can enhance the trilineage differentiation potential of MSCs; and further explained the mechanism behind.Methods: We used histological staining to screen out the nsPEFs parameters that promoted the trilineage differentiation potential of MSCs, and further proved the effect of nsPEFs by detecting the functional genes. In order to explore the corresponding mechanism, we examined the expression of pluripotency genes and the methylation status of their promoters. Finally, we targeted the DNA methyltransferase which was affected by nsPEFs. Results: The trilineage differentiation of bone marrow derived MSCs was significantly enhanced in vitro by simply pre-treated with 5 pulses of nsPEFs stimulation (energy levels as 10 ns, 20 kV/cm; 100 ns, 10 kV/cm), due to that the nsPEFs demethylated the promoters of stem cell pluripotency genes OCT4 and NANOG through instantaneous downregulation of DNA methylation transferase 1 (DNMT1), thereby increased the expression of OCT4 and NANOG for up to 3 days, and created a treatment window period of stem cells.Conclusions: In summary, nsPEFs can enhance MSCs differentiation via the epigenetic regulation, and could be a safe and effective strategy for future stem cell application

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

2019 ◽  
Vol 20 (20) ◽  
pp. 5091 ◽  
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.

Abstract 11: Xenogen-free In Vitro Differentiation and Expansion of Human Pluripotent Stem Cell-Derived Cardiovascular Progenitor Cells

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Xianmei Meng ◽  
Anne Knopf ◽  
Agustin Vega-Crespo ◽  
James Byrne ◽  
Ben Van Handel ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Pluripotent Stem Cell ◽  
Single Cells ◽  
Embryonic Stem ◽  
Human Pluripotent Stem Cell ◽  
Differentiation Potential ◽  
Cell Based Therapy ◽  
Trilineage Differentiation

Background: Human pluripotent stem cell-derived cardiovascular progenitor cells (hPSC-CPCs) represent a tractable option for cell-based therapy for heart disease. However, to be clinically relevant, these cells must be derived under good manufacturing practices (GMP)-compatible conditions and produced in great enough quantities to treat adult patients. Here we sought to demonstrate for the first time the generation and expansion of clinically relevant numbers of hPSC-CPCs in xenogen-free protocol. Methods and Results: GMP-grade human induced pluripotent stem cells (GMP-hiPSCs) and human embryonic stem cells (H1 and H9) were dissociated into single cells and cultured in low attachment dishes to differentiate into CPCs in StemPro medium including small molecules and human cytokines with high efficiency of 86%, 80% and 66% for GMP-hiPSCs, H1 and H9, respectively (Figure 1). All hPSC-CPCs possessed trilineage differentiation potentials, as shown by differentiation into endothelial and smooth muscle cells and functional cardiomyocytes (Figure 2). Moreover, sorted hPSC-CPCs expanded >5 fold in 10 days in xenogen-free conditions while still maintaining trilineage differentiation potential and an efficiency of ~70% (Figure 3). Conclusions: Here we demonstrate a xenogeny-free CPC derivation and expansion protocol that can generate clinically relevant numbers of GMP-grade cardiovascular progenitors that could be used in a clinical setting.

Metabolic Regulation and Related Molecular Mechanisms in Various Stem Cell Functions

2020 ◽  
Vol 15 (6) ◽  
pp. 531-546 ◽  
Author(s):  
Hwa-Yong Lee ◽  
In-Sun Hong
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Oxidative Phosphorylation ◽  
Metabolic Pathways ◽  
Critical Role ◽  
The Self ◽  
Specific Cell ◽  
Differentiation Potential ◽  
Self Renewal ◽  
Cell Functions

Recent studies on the mechanisms that link metabolic changes with stem cell fate have deepened our understanding of how specific metabolic pathways can regulate various stem cell functions during the development of an organism. Although it was originally thought to be merely a consequence of the specific cell state, metabolism is currently known to play a critical role in regulating the self-renewal capacity, differentiation potential, and quiescence of stem cells. Many studies in recent years have revealed that metabolic pathways regulate various stem cell behaviors (e.g., selfrenewal, migration, and differentiation) by modulating energy production through glycolysis or oxidative phosphorylation and by regulating the generation of metabolites, which can modulate multiple signaling pathways. Therefore, a more comprehensive understanding of stem cell metabolism could allow us to establish optimal culture conditions and differentiation methods that would increase stem cell expansion and function for cell-based therapies. However, little is known about how metabolic pathways regulate various stem cell functions. In this context, we review the current advances in metabolic research that have revealed functional roles for mitochondrial oxidative phosphorylation, anaerobic glycolysis, and oxidative stress during the self-renewal, differentiation and aging of various adult stem cell types. These approaches could provide novel strategies for the development of metabolic or pharmacological therapies to promote the regenerative potential of stem cells and subsequently promote their therapeutic utility.

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