scholarly journals STEM-15. SMALL BUT FIERCE: THE ROLE OF EXTRACELLULAR VESICLES IN MESENCHYMAL TRANSITION AND THERAPEUTIC RESISTANCE IN GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii199-ii199
Author(s):  
Markus Schweiger ◽  
Mao Li ◽  
Renata Fleming ◽  
Elie Tabet ◽  
Thomas Würdinger ◽  
...  

Abstract Glioblastoma (GBM) is a dismal disease and despite optimal treatment, long-term survival remains uncommon. Molecular classification revealed three distinct GBM subgroups and has helped to shine light on the tumor’s inter/intratumoral heterogeneity. Interestingly, recent evidence shows plasticity between these subtypes in which the proneural (PN) glioma stem-like cells undergo transition into the more aggressive mesenchymal (MES) subtype leading to therapeutic resistance. Extracellular vesicles (EVs) are considered a heterogeneous group of membrane-limited vesicles secreted by nearly every cell. In the context of GBM, these biological nanoparticles act as multifunctional signaling complexes and play an important role in intercellular communication allowing cancer cells to exchange information with each other, the tumor microenvironment, and distant cells. We show that MES cells derived EVs modulate PN cells to increase migratory potential, stemness, invasiveness, aggressiveness, and therapeutic resistance by inducing mesenchymal transition through NF-KB/STAT3 signaling. Furthermore, we shine light on the role of EVs derived from irradiated GBM cells and their potential impact on microglia and resulting treatment resistance.

2020 ◽  
Vol 4 (12) ◽  
pp. 2070121
Author(s):  
Markus W. Schweiger ◽  
Mao Li ◽  
Alberta Giovanazzi ◽  
Renata L. Fleming ◽  
Elie I. Tabet ◽  
...  

2020 ◽  
Vol 4 (12) ◽  
pp. 1900312 ◽  
Author(s):  
Markus W. Schweiger ◽  
Mao Li ◽  
Alberta Giovanazzi ◽  
Renata L. Fleming ◽  
Elie I. Tabet ◽  
...  

2020 ◽  
Vol 20 ◽  
Author(s):  
Qionghui Wu ◽  
Haidong Wei ◽  
Wenbo Meng ◽  
Xiaodong Xie ◽  
Zhenchang Zhang ◽  
...  

: Annexin, a calcium-dependent phospholipid binding protein, can affect tumor cell adhesion, proliferation, apoptosis, invasion and metastasis, as well as tumor neovascularization in different ways. Recent studies have shown that annexin exists not only as an intracellular protein in tumor cells, but also in different ways to be secret outside the cell as a “crosstalk” tool for tumor cells and tumor microenvironment, thus playing an important role in the development of tumors, such as participating in epithelial-mesenchymal transition, regulating immune cell behavior, promoting neovascularization and so on. The mechanism of annexin secretion in the form of extracellular vesicles and its specific role is still unclear. This paper summarizes the main role of annexin secreted into the extracellular space in the form of extracellular vesicles in tumorigenesis and drug resistance and analyzes its possible mechanism.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 767
Author(s):  
Courtney Davis ◽  
Sean I. Savitz ◽  
Nikunj Satani

Ischemic stroke is a debilitating disease and one of the leading causes of long-term disability. During the early phase after ischemic stroke, the blood-brain barrier (BBB) exhibits increased permeability and disruption, leading to an influx of immune cells and inflammatory molecules that exacerbate the damage to the brain tissue. Mesenchymal stem cells have been investigated as a promising therapy to improve the recovery after ischemic stroke. The therapeutic effects imparted by MSCs are mostly paracrine. Recently, the role of extracellular vesicles released by these MSCs have been studied as possible carriers of information to the brain. This review focuses on the potential of MSC derived EVs to repair the components of the neurovascular unit (NVU) controlling the BBB, in order to promote overall recovery from stroke. Here, we review the techniques for increasing the effectiveness of MSC-based therapeutics, such as improved homing capabilities, bioengineering protein expression, modified culture conditions, and customizing the contents of EVs. Combining multiple techniques targeting NVU repair may provide the basis for improved future stroke treatment paradigms.


2021 ◽  
pp. 0739456X2110282
Author(s):  
Maria Watson

Local businesses are important for recovering communities, yet program analyses of the effectiveness of Federal disaster loans—particularly for businesses—are limited and contradictory. This study looks at the role U.S. Small Business Administration (SBA) Disaster Loans played in the long-term survival of small businesses in Galveston County, Texas after the 2008 Hurricane Ike. This research uses quasi-experimental design, matching methods, and conditional logistic regression to tease out the effect of the loan from potential confounding factors. The results show that businesses that received a disaster loan were significantly more likely to survive than their controls, and businesses that moved were also more likely to survive.


2016 ◽  
Vol 23 (6) ◽  
pp. 1003-1008 ◽  
Author(s):  
Antonio Macciò ◽  
Paraskevas Kotsonis ◽  
Giacomo Chiappe ◽  
Luca Melis ◽  
Fausto Zamboni ◽  
...  

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Guang-Yan Cai

Abstract Background and Aims The mechanism of renal interstitial fibrosis occurs with kidney aging is unknown. Caloric restriction and caloric restriction mimetics (CRM) alleviate aging-related-fibrosis. The aim of this study is to investigate whether extracellular microvesicles (EVs) derived from senescent cells facilitate fibrosis development in aging kidney and the potential signalling pathway involved in the process. Method In this study, animal experiments included 3-mon-old ad libitum(YAL) rats, 24-mon-old ad libitum(OAL) rats and 24-mon-old caloric restriction(OCR) rats, which was given 70% of OAL’s for 8 months. Senescent cells were induced in proximal tubular epithelial cells(PTCs) by high glucose and further treated with resveratrol as CRM. The expression of miR-21, peroxisome proliferator-activated receptor(PPARα), hypoxia-inducible factor(HIF1α) in the kidney of rats and PTCs were examined. Epithelial to mesenchymal transition (EMT) and the related signalling pathway were detected by up- or down-regulation of miR-21, respectively. Results Long-term caloric restriction ameliorated senescent changes and aging-related fibrosis in aged ad libitum rat kidney. Caloric restriction blunted the increased expressions of miR-21 and HIF1α, the decreased expression of PPARα in renal tissue of old rats. High glucose induced PTCs senesence phenotype and EMT. miR-21 was detected in extracellular vesicles secreted by senescent PTC cells. CRMs resveratrol prevented EMT through downregulation of miR-21 in extracellular vesicles from the senescent PTC cells. Further, inhibiting miR-21 of donor senescent cells prevented the occurrence of EMT in recipient PTC cells. Finally, miR-21 induced EMT mainly through targeting PPARα protein and enhancing HIF1α expression. Conclusion This study demonstrated that miR-21-containing extracellular microvesicles derived from the senescent cells could facilitate tubular phenotype transition of neighbouring PTC cells via PPARα-HIF1α signalling pathway. Long-term caloric restriction and caloric restriction mimetics alleviate aging-related renal fibrosis through downregulation of miR-21 excretion.


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