Enhanced Induction of Definitive Endoderm Differentiation of Mouse Embryonic Stem Cells in Simulated Microgravity

Oss-Ronen, Liat; Redden, Robert A.; Lelkes, Peter I.

doi:10.1089/scd.2020.0097

Cited by 10 publications

(10 citation statements)

References 76 publications

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“…Microgravity has a positive effect in some ways. Mouse embryonic stem cell (mESC) cultured in a rotating bioreactor under simulated microgravity conditions can differentiate towards stereotyped endoderm, and these cells can further differentiate into cells from other related organs such as the pancreas, liver, and thyroid [ 79 ]. Simulated microgravity also promoted the proliferation and matrix production of tissue-engineered human chondrocyte-like cells [ 80 ].…”

Section: Mechanical Microenvironment For Stem Cell Growthmentioning

confidence: 99%

How the mechanical microenvironment of stem cell growth affects their differentiation: a review

Zhang

Wang

2022

Stem Cell Res Ther

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Stem cell differentiation is of great interest in medical research; however, specifically and effectively regulating stem cell differentiation is still a challenge. In addition to chemical factors, physical signals are an important component of the stem cell ecotone. The mechanical microenvironment of stem cells has a huge role in stem cell differentiation. Herein, we describe the knowledge accumulated to date on the mechanical environment in which stem cells exist, which consists of various factors, including the extracellular matrix and topology, substrate stiffness, shear stress, hydrostatic pressure, tension, and microgravity. We then detail the currently known signalling pathways that stem cells use to perceive the mechanical environment, including those involving nuclear factor-kB, the nicotinic acetylcholine receptor, the piezoelectric mechanosensitive ion channel, and hypoxia-inducible factor 1α. Using this information in clinical settings to treat diseases is the goal of this research, and we describe the progress that has been made. In this review, we examined the effects of mechanical factors in the stem cell growth microenvironment on stem cell differentiation, how mechanical signals are transmitted to and function within the cell, and the influence of mechanical factors on the use of stem cells in clinical applications.

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Section: Mechanical Microenvironment For Stem Cell Growthmentioning

confidence: 99%

How the mechanical microenvironment of stem cell growth affects their differentiation: a review

Zhang

Wang

2022

Stem Cell Res Ther

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“…Furthermore, another group reported that microgravity and 3D culture enhanced the differentiation of cardiac progenitor from human ESCs and iPSCs with the production of enriched cardiomyocytes (99% purity) and high viability [99]. Regarding endodermal differentiation, the culturing embryoid bodies were placed in a rotary bioreactor, which simulates microgravity, and upregulated all of the definitive endoderm markers as Foxa2 and Sox17 in mouse ESCs, indicating that this biophysical stimulation enhanced directed endodermal differentiation [100]. A rotating bioreactor with a biodegradable polymer scaffold also can yield functional and transplantable hepatocyte from mouse ESCs [101].…”

Section: Effect Of Physical Stimuli On Directed Differentiation Of Pluripotent Stem Cellsmentioning

confidence: 99%

Response of Pluripotent Stem Cells to Environmental Stress and Its Application for Directed Differentiation

Kaitsuka

Hakim

2021

Biology

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Pluripotent stem cells have unique characteristics compared to somatic cells. In this review, we summarize the response to environmental stresses (hypoxic, oxidative, thermal, and mechanical stresses) in embryonic stem cells (ESCs) and their applications in the differentiation methods directed to specific lineages. Those stresses lead to activation of each specific transcription factor followed by the induction of downstream genes, and one of them regulates lineage specification. In short, hypoxic stress promotes the differentiation of ESCs to mesodermal lineages via HIF-1α activation. Concerning mechanical stress, high stiffness tends to promote mesodermal differentiation, while low stiffness promotes ectodermal differentiation via the modulation of YAP1. Furthermore, each step in the same lineage differentiation favors each appropriate stiffness of culture plate; for example, definitive endoderm favors high stiffness, while pancreatic progenitor favors low stiffness during pancreatic differentiation of human ESCs. Overall, treatments utilizing those stresses have no genotoxic or carcinogenic effects except oxidative stress; therefore, the differentiated cells are safe and could be useful for cell replacement therapy. In particular, the effect of mechanical stress on differentiation is becoming attractive for the field of regenerative medicine. Therefore, the development of a stress-mediated differentiation protocol is an important matter for the future.

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“…ESCs can differentiate into different types of cells in the body. Multiple studies have shown that microgravity can affect the differentiation of ESCs ( Lei et al, 2014 ; Blaber et al, 2015 ; Jha et al, 2016 ; Shinde et al, 2016 ; Lei et al, 2018 ; Mattei et al, 2018 ; Oss-Ronen et al, 2020 ). For example, the expression of mesoderm marker gene Brachyury (T) in embryoid bodies (EBs) is significantly higher under microgravity than under 1G ground conditions ( Lei et al, 2018 ; Oss-Ronen et al, 2020 ), indicating that microgravity promotes the differentiation of ESCs into mesoderm.…”

Section: Effects Of Microgravity On Esc Differentiationmentioning

confidence: 99%

“…Multiple studies have shown that microgravity can affect the differentiation of ESCs ( Lei et al, 2014 ; Blaber et al, 2015 ; Jha et al, 2016 ; Shinde et al, 2016 ; Lei et al, 2018 ; Mattei et al, 2018 ; Oss-Ronen et al, 2020 ). For example, the expression of mesoderm marker gene Brachyury (T) in embryoid bodies (EBs) is significantly higher under microgravity than under 1G ground conditions ( Lei et al, 2018 ; Oss-Ronen et al, 2020 ), indicating that microgravity promotes the differentiation of ESCs into mesoderm. A study from NASA (STS-131 mission on the space shuttle Discovery) showed that ESCs differentiate more readily into contractile cardiomyocytes under microgravity conditions ( Blaber et al, 2015 ).…”

Section: Effects Of Microgravity On Esc Differentiationmentioning

confidence: 99%

“…In addition to the increase in mesoderm differentiation, the expression levels of endoderm markers, such as FoxA2 , Sox17 , and CxCr4 , are also significantly up-regulated in differentiated ESCs under microgravity, indicating that microgravity may promote the differentiation of ESCs into endoderm ( Oss-Ronen et al, 2020 ). Consistently, Lei et al (2014) showed that microgravity promotes the differentiation of mouse ESCs into endoderm by activating the Wnt pathway but inhibits the differentiation of ESCs into neuroectoderm.…”

Section: Effects Of Microgravity On Esc Differentiationmentioning

confidence: 99%

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Effects of Microgravity on Early Embryonic Development and Embryonic Stem Cell Differentiation: Phenotypic Characterization and Potential Mechanisms

Lei

et al. 2021

Front. Cell Dev. Biol.

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With the development of science and technology, mankind’s exploration of outer space has increased tremendously. Settling in outer space or on other planets could help solve the Earth’s resource crisis, but such settlement will first face the problem of reproduction. There are considerable differences between outer space and the Earth’s environment, with the effects of gravity being one of the most significant. Studying the possible effects and underlying mechanisms of microgravity on embryonic stem cell (ESC) differentiation and embryonic development could help provide solutions to healthy living and reproduction in deep space. This article summarizes recent research progress on the effects of microgravity on ESCs and early embryonic development and proposes hypotheses regarding the potential mechanisms. In addition, we discuss the controversies and key questions in the field and indicate directions for future research.

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Enhanced Induction of Definitive Endoderm Differentiation of Mouse Embryonic Stem Cells in Simulated Microgravity

Cited by 10 publications

References 76 publications

How the mechanical microenvironment of stem cell growth affects their differentiation: a review

How the mechanical microenvironment of stem cell growth affects their differentiation: a review

Response of Pluripotent Stem Cells to Environmental Stress and Its Application for Directed Differentiation

Effects of Microgravity on Early Embryonic Development and Embryonic Stem Cell Differentiation: Phenotypic Characterization and Potential Mechanisms

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