Systematic Analysis of mRNA and miRNA Expression of 3D-Cultured Neural Stem Cells (NSCs) in Spaceflight

Cui, Yi; Han, Jin Soo; Xiao, Zhifeng; Qi, Yiduo; Zhao, Yannan; Chen, Bing; Fang, Yongxiang; Liu, Sumei; Wu, Xianming; Dai, Jianwu

doi:10.3389/fncel.2017.00434

Cited by 14 publications

(15 citation statements)

References 79 publications

(81 reference statements)

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“…The culturing environment is one of the most important pivotal factors that in uence cell function and its potential therapeutic effects following transplantation. Our previous ndings demonstrated that NSCs tend to differentiate into neurons and that glial differentiation is inhibited during space ight [11].…”

Section: Discussionmentioning

confidence: 98%

The Rotary Cell Culture System increases NTRK3 expression and promotes neuronal differentiation and migratory ability of neural stem cells cultured on collagen sponge

Cui¹,

Yin

Zhao

et al. 2021

Preprint

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Background: Recently, neural stem cell (NSC) therapy has shown promise for the treatment of many neurological diseases. Enhancing the quality of implanted cells and improving therapeutic efficacy are currently research hotspots. In this study, we attempted to evaluate whether the combination of 3D cell culturing with the RCCS is the optimal method to improve the neural differentiation ability of NSCs and produce appropriate cells for treating neurological diseases.Methods: We performed mRNA and miRNA sequencing to characterize NSCs cultured on a collagen sponge in the RCCS. The luciferase assay and Western blot revealed a direct regulatory role between let-7i-5p and neurotrophic receptor tyrosine kinase 3 (NTRK3). The neural differentiation markers Tuj1 and Map2 were detected by immunofluorescence staining, and the migratory ability of NSCs was detected both in vitro and in spinal cord injury animals. Results: NTRK3 expression was elevated in NSCs cultured on collagen sponge in the RCCS. Furthermore, increased NTRK3 expression was regulated by the downregulation of let-7i-5p. Compared with traditionally cultured NSCs, the NSCs cultured on collagen sponge in the RCCS exhibited better neuronal differentiation and migratory ability, especially in the presence of NT-3.Conclusions: As the biological properties and quality of transplanted cells are critical for therapeutic success, the RCCS combined with collagen sponge shows promise for clinical applications in the future.

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Section: Discussionmentioning

confidence: 98%

The Rotary Cell Culture System increases NTRK3 expression and promotes neuronal differentiation and migratory ability of neural stem cells cultured on collagen sponge

Cui¹,

Yin

Zhao

et al. 2021

Preprint

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“…Neural stem cells isolated from rat telencephalon tissues cultured in an automated bioreactor onboard SJ-10 satellite maintained their potential and displayed a transcription profile similar to that of the control, but they tended to divide less and were more prone to enter neuronal differentiation [15]. Interestingly, neural stem cells exposed to microgravity tended to differentiate into astrocytes on transplantation [16].…”

Section: Introductionmentioning

confidence: 88%

“…To some extent, MG cells resemble neural stem cells [6], which have been studied in space conditions by other groups. Murine neural stem cells, cultivated in a 3D bioreactor in space, maintained their ''stemness,'' even displayed upregulation of stem cell transcription factors Sox2 and Pax6, but proliferated slower than in 1 g and underwent neural differentiation more readily [15]. Global transcriptomic analysis revealed the leading role of the WNT signaling pathway in these processes.…”

Section: Müller Gliamentioning

confidence: 99%

Behavior of Stem-Like Cells, Precursors for Tissue Regeneration in Urodela, Under Conditions of Microgravity

Grigoryan

Radugina

2019

Stem Cells and Development

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We summarize data from our experiments on stem-like cell-dependent regeneration in amphibians in microgravity. Considering its deleterious effect on many tissues, we asked whether microgravity is compatible with reparative processes, specifically activation and proliferation of source cells. Experiments were conducted using tailed amphibians, which combine profound regenerative capabilities with high robustness, allowing an in vivo study of lens, retina, limb, and tail regeneration in challenging settings of spaceflight. Microgravity promoted stem-like cell proliferation to a varying extent (up to 2-fold), and it seemed to speed up source cell dedifferentiation, as well as sequential differentiation in retina, lens, and limb, leading to formation of bigger and more developed regenerates than in 1g controls. It also promoted proliferation and hypertrophy of Müller glial cells, eliciting a response similar to reactive gliosis. A significant increase in stem-like cell proliferation was mostly beneficial for regeneration and only in rare cases caused moderate tissue growth abnormalities. It is important that microgravity yielded a lasting effect even if applied before operations. We hypothesize on the potential mechanisms of gravity-dependent changes in stem-like cell behavior, including fibroblast growth factor 2 signaling pathway and heat shock proteins, which were affected in our experimental settings. Taken together, our data indicate that microgravity does not disturb the natural regenerative potential of newt stem-like cells, and, depending on the system, even stimulates their dedifferentiation, proliferation, and differentiation. We discuss these data along with publications on mammalian stem cell behavior in vitro and invertebrate regeneration in vivo in microgravity. In vivo data are very scarce and require further research using contemporary methods of cell behavior analysis to elucidate mechanisms of stem cell response to altered gravity. They are relevant for both practical applications, such as managing human reparative responses in spaceflight, and fundamental understanding of stem cell biology.

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“…Our previous studies have demonstrated that the conditions in outer space promote neuronal differentiation of NSCs [9]. As microgravity is one of the key factors of outer space [10,11], this present study investigated the influence of simulated microgravity on three-dimensional (3D) cultured NSCs with a dynamic 3D Rotary Cell Culture System (RCCS).…”

Section: Introductionmentioning

confidence: 99%

The Rotary Cell Culture System increases NTRK3 Expression and Promotes Neuronal Differentiation and Migratory Ability of Neural Stem Cells Cultured on Collagen Sponge

Cui¹,

Yin

Zhao

et al. 2020

Preprint

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Background Recently, neural stem cell (NSC) therapy has shown promise for the treatment of many neurological diseases. Enhancing the quality of implanted cells and improving therapeutic efficacy are currently research hotspots. It has been reported that collagen sponge material provided sufficient room for cell growth in all directions, promoted the absorption of nutrients and removal of wastes. And also, the Rotary Cell Culture System (RCCS), which mimics the microgravity environment, can be used to culture cells for tissue engineering. Materials and methods We performed the mRNA and miRNA sequencing to elucidate the regulatory mechanism of NSCs cultured on the collagen sponge in RCCS system. The luciferase assay and Western blot revealed a direct regulatory role between let-7i-5p and NTRK3. And then, the neural differentiation maker Tuj1 and Map2 were detected by immunofluorescence staining. In the meantime, the migratory ability of NSCs was detected both in vitro and in spinal cord injury animals. Results In this study, we demonstrated that the expression of neurotrophic receptor tyrosine kinase 3 (NTRK3; also called TrkC) was elevated in NSCs cultured on collagen sponge in the RCCS system. Furthermore, increased NTRK3 expression was regulated by the downregulation of let-7i-5p. Compared to traditionally cultured NSCs, the NSCs cultured on collagen sponge in the RCCS system exhibited better neuronal differentiation and migratory ability, especially in the presence of NT-3. Conclusions As the biological properties and quality of transplanted cells are critical for therapeutic success, the RCCS system combined with collagen sponge culture system show promise for applications in clinical practice in the future.

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Systematic Analysis of mRNA and miRNA Expression of 3D-Cultured Neural Stem Cells (NSCs) in Spaceflight

Cited by 14 publications

References 79 publications

The Rotary Cell Culture System increases NTRK3 expression and promotes neuronal differentiation and migratory ability of neural stem cells cultured on collagen sponge

The Rotary Cell Culture System increases NTRK3 expression and promotes neuronal differentiation and migratory ability of neural stem cells cultured on collagen sponge

Behavior of Stem-Like Cells, Precursors for Tissue Regeneration in Urodela, Under Conditions of Microgravity

The Rotary Cell Culture System increases NTRK3 Expression and Promotes Neuronal Differentiation and Migratory Ability of Neural Stem Cells Cultured on Collagen Sponge

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