scholarly journals Dissecting the Effect of a 3D Microscaffold on the Transcriptome of Neural Stem Cells with Computational Approaches: A Focus on Mechanotransduction

2020 ◽  
Vol 21 (18) ◽  
pp. 6775 ◽  
Author(s):  
Federica Rey ◽  
Cecilia Pandini ◽  
Bianca Barzaghini ◽  
Letizia Messa ◽  
Toniella Giallongo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Mechanical Stimuli ◽  
Rna Seq ◽  
3D Cell Cultures ◽  
Different Types ◽  
Strongly Connected ◽  
Molecular Bases

3D cell cultures are becoming more and more important in the field of regenerative medicine due to their ability to mimic the cellular physiological microenvironment. Among the different types of 3D scaffolds, we focus on the Nichoid, a miniaturized scaffold with a structure inspired by the natural staminal niche. The Nichoid can activate cellular responses simply by subjecting the cells to mechanical stimuli. This kind of influence results in different cellular morphology and organization, but the molecular bases of these changes remain largely unknown. Through RNA-Seq approach on murine neural precursors stem cells expanded inside the Nichoid, we investigated the deregulated genes and pathways showing that the Nichoid causes alteration in genes strongly connected to mechanobiological functions. Moreover, we fully dissected this mechanism highlighting how the changes start at a membrane level, with subsequent alterations in the cytoskeleton, signaling pathways, and metabolism, all leading to a final alteration in gene expression. The results shown here demonstrate that the Nichoid influences the biological and genetic response of stem cells thorough specific alterations of cellular signaling. The characterization of these pathways elucidates the role of mechanical manipulation on stem cells, with possible implications in regenerative medicine applications.

scholarly journals Chorionic Villous Mesenchymal Stem Cells Derived Exosomes Deliver miR-135b-5p to Trophoblasts, Promoting their Proliferation and Invasion by Targeting TXNIP via β-Catenin Pathway

2020 ◽  
Author(s):  
Yijing Chu ◽  
Yan Zhang ◽  
Guoqiang Gao ◽  
Jun Zhou ◽  
Yang Lv ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tissue Injury ◽  
Luciferase Reporter ◽  
Rna Seq ◽  
Qrt Pcr ◽  
Reporter Assays ◽  
Pcr Assays ◽  
Proliferation And Invasion

Abstract Background: Human chorionic villous mesenchymal stem cells (CV-MSCs) are found to be a promising and effective treatment for tissue injury. Trophoblast dysfunction during pregnancies is significantly involved in the pathogenesis of preeclampsia (PE). This work was to understand how CV-MSCs regulated trophoblast function. Methods: In this study, we treated trophoblasts with CV-MSC-derived exosomes and RNA-seq analysis was used to understand the changes in trophoblasts. We examined the levels of TXNIP and β-catenin in trophoblasts by immunohistochemistry, western blot and qRT-PCR assays. Luciferase reporter assays and qRT-PCR assays were used to understand the role of miR135b-5p in the effects of CV-MSC-derived exosomes. The growth and invasion of trophoblasts was evaluated with the CCK-8 and transwell assays. Results: The treatment markedly enhanced the trophoblast proliferation and invasion. Furthermore, a significant decrease of TXNIP expression and inactivation of the β-catenin pathway in CV-MSCs exosomes-treated trophoblasts was observed. Consistent with these findings, TXNIP inhibition exhibited the same effect of promoting trophoblast proliferation and invasion as induced by CV-MSC-derived exosomes, also with the accompaniment of inactivation of β-catenin pathway. In addition, overexpression of TXNIP activated the β-catenin pathway in trophoblasts, and reduced the proliferation and invasion of trophoblasts. Importantly, miR135b-5p was found to be highly expressed in CV-MSC exosomes and interact with TXNIP. The miR-135b-5p overexpression significantly elevated the proliferation and invasion of trophoblasts, which could be attenuated by TXNIP overexpression. Conclusion: Our results suggest that TXNIP-dependent β-catenin pathway inactivation mediated by miR135b-5p which is delivered by CV-MSC-derived exosomes could promote the proliferation and invasion of trophoblasts.

scholarly journals Cell Populations Expressing Stemness-Associated Markers in Vascular Anomalies

2021 ◽  
Vol 7 ◽  
Author(s):  
Ethan J. Kilmister ◽  
Lauren Hansen ◽  
Paul F. Davis ◽  
Sean R. R. Hall ◽  
Swee T. Tan
Keyword(s):  
Stem Cells ◽  
Side Effects ◽  
Embryonic Stem ◽  
Gene Mutations ◽  
Vascular Anomalies ◽  
Vascular Tumors ◽  
Cell Populations ◽  
Adrenergic Blockade ◽  
Different Types

Treatment of vascular anomalies (VAs) is mostly empirical and, in many instances unsatisfactory, as the pathogeneses of these heterogeneous conditions remain largely unknown. There is emerging evidence of the presence of cell populations expressing stemness-associated markers within many types of vascular tumors and vascular malformations. The presence of these populations in VAs is supported, in part, by the observed clinical effect of the mTOR inhibitor, sirolimus, that regulates differentiation of embryonic stem cells (ESCs). The discovery of the central role of the renin-angiotensin system (RAS) in regulating stem cells in infantile hemangioma (IH) provides a plausible explanation for its spontaneous and accelerated involution induced by β-blockers and ACE inhibitors. Recent work on targeting IH stem cells by inhibiting the transcription factor SOX18 using the stereoisomer R(+) propranolol, independent of β-adrenergic blockade, opens up exciting opportunities for novel treatment of IH without the β-adrenergic blockade-related side effects. Gene mutations have been identified in several VAs, involving mainly the PI3K/AKT/mTOR and/or the Ras/RAF/MEK/ERK pathways. Existing cancer therapies that target these pathways engenders the exciting possibility of repurposing these agents for challenging VAs, with early results demonstrating clinical efficacy. However, there are several shortcomings with this approach, including the treatment cost, side effects, emergence of treatment resistance and unknown long-term effects in young patients. The presence of populations expressing stemness-associated markers, including transcription factors involved in the generation of induced pluripotent stem cells (iPSCs), in different types of VAs, suggests the possible role of stem cell pathways in their pathogenesis. Components of the RAS are expressed by cell populations expressing stemness-associated markers in different types of VAs. The gene mutations affecting the PI3K/AKT/mTOR and/or the Ras/RAF/MEK/ERK pathways interact with different components of the RAS, which may influence cell populations expressing stemness-associated markers within VAs. The potential of targeting these populations by manipulating the RAS using repurposed, low-cost and commonly available oral medications, warrants further investigation. This review presents the accumulating evidence demonstrating the presence of stemness-associated markers in VAs, their expression of the RAS, and their interaction with gene mutations affecting the PI3K/AKT/mTOR and/or the Ras/RAF/MEK/ERK pathways, in the pathogenesis of VAs.

scholarly journals Study on the role of JAK/STAT signaling pathway during chicken spermatogonial stem cells generation based on RNA-Seq

2015 ◽  
Vol 14 (5) ◽  
pp. 939-948 ◽  
Author(s):  
Lei ZHANG ◽  
Qi-sheng ZUO ◽  
Dong LI ◽  
Chao LIAN ◽  
Kamel E Ahmed ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathway ◽  
Spermatogonial Stem Cells ◽  
Rna Seq ◽  
Stat Signaling

Mesenchymal Stem Cell Derived-Exosomes as Effective Factors in Reducing Cytokine Storm Symptoms of COVID-19

2021 ◽  
Vol 28 ◽  
Author(s):  
Amir Hossein Kheirkhah ◽  
Seyed Hossein Shahcheraghi ◽  
Malihe lotfi ◽  
Marzieh lotfi ◽  
Sanaz Raeisi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune System ◽  
Host Immune System ◽  
Cytokine Storm ◽  
Infection Transmission ◽  
Effective Factors ◽  
Different Types ◽  
Immune System Modulation

: Given that conventional therapies are ineffective for COVID-19, obtained exosomes from stem cells have been proposed as a sustainable and effective treatment. Exosomes are subsets with lengths between 30 and 100 nanometers, and they can be secreted by different cells. Exosomes are containing different types of miRNAs, mRNAs, and different proteins. The role of immune system modulation of exosomes of mesenchymal stem cells has been studied and confirmed in more than one study. Exosome miRNAs detect and reduce cytokines that cause cytokine storms such as IL-7, IL-2, IL-6, etc. These miRNAs include miR-21, miR-24, miR-124, miR-145, etc. The risks associated with treatment with exosomes from different cells are relatively small compared to other treatments because transplanted cells do not stimulate the host immune system and also has reduced infection transmission. Due to the ineffectiveness of existing drugs in reducing inflammation and preventing cytokine storms, the use of immune-boosting systems may be suggested as another way to control cytokine storm.

scholarly journals The Role of Tumor-Associated Macrophages in Leukemia

2019 ◽  
Vol 143 (2) ◽  
pp. 112-117 ◽  
Author(s):  
Yueyang Li ◽  
M. James You ◽  
Yaling Yang ◽  
Dongzhi Hu ◽  
Chen Tian
Keyword(s):  
Stem Cells ◽  
Innate Immunity ◽  
Mesenchymal Stem Cells ◽  
Immune Cells ◽  
Leukemia Cell ◽  
Tumor Associated Macrophages ◽  
Intrinsic Factors ◽  
Different Types ◽  
Tumor Growth And Metastasis

In addition to intrinsic factors, leukemia cell growth is influenced by the surrounding nonhematopoietic cells in the leukemic microenvironment, including fibroblasts, mesenchymal stem cells, vascular cells, and various immune cells. Despite the fact that macrophages are an important component of human innate immunity, tumor-associated macrophages (TAMs) have long been considered as an accomplice promoting tumor growth and metastasis. TAMs are activated by an abnormal malignant microenvironment, polarizing into a specific phenotype and participating in tumor progression. TAMs that exist in the microenvironment of different types of leukemia are called leukemia-associated macrophages (LAMs), which are reported to be associated with the progression of leukemia. This review describes the role of LAMs in different leukemia subtypes.

scholarly journals Concise Review: Multifaceted Characterization of Human Mesenchymal Stem Cells for Use in Regenerative Medicine

2017 ◽  
Vol 6 (12) ◽  
pp. 2173-2185 ◽  
Author(s):  
Rebekah M. Samsonraj ◽  
Michael Raghunath ◽  
Victor Nurcombe ◽  
James H. Hui ◽  
Andre J. van Wijnen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Regenerative Medicine ◽  
Human Mesenchymal Stem Cells ◽  
Concise Review
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