scholarly journals NSCs Under Strain—Unraveling the Mechanoprotective Role of Differentiating Astrocytes in a Cyclically Stretched Coculture With Differentiating Neurons

2021 ◽  
Vol 15 ◽  
Author(s):  
Jella-Andrea Abraham ◽  
Stefan Blaschke ◽  
Samar Tarazi ◽  
Georg Dreissen ◽  
Sabine U. Vay ◽  
...  

The neural stem cell (NSC) niche is a highly vascularized microenvironment that supplies stem cells with relevant biological and chemical cues. However, the NSCs’ proximity to the vasculature also means that the NSCs are subjected to permanent tissue deformation effected by the vessels’ heartbeat-induced pulsatile movements. Cultivating NSCs under common culture conditions neglects the—yet unknown—influence of this cyclic mechanical strain on neural stem cells. Under the hypothesis that pulsatile strain should affect essential NSC functions, a cyclic uniaxial strain was applied under biomimetic conditions using an in-house developed stretching system based on cross-linked polydimethylsiloxane (PDMS) elastomer. While lineage commitment remained unaffected by cyclic deformation, strain affected NSC quiescence and cytoskeletal organization. Unexpectedly, cyclically stretched stem cells aligned in stretch direction, a phenomenon unknown for other types of cells in the mammalian organism. The same effect was observed for young astrocytes differentiating from NSCs. In contrast, young neurons differentiating from NSCs did not show mechanoresponsiveness. The exceptional orientation of NSCs and young astrocytes in the stretch direction was blocked upon RhoA activation and went along with a lack of stress fibers. Compared to postnatal astrocytes and mature neurons, NSCs and their young progeny displayed characteristic and distinct mechanoresponsiveness. Data suggest a protective role of young astrocytes in mixed cultures of differentiating neurons and astrocytes by mitigating the mechanical stress of pulsatile strain on developing neurons.

2013 ◽  
Vol 144 (5) ◽  
pp. S-478
Author(s):  
Michael Gonzales ◽  
Xuxia Gao ◽  
Yanna Cao ◽  
Hasen Xue ◽  
Judith Aronson ◽  
...  

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Kristin M French ◽  
Marcos J Fierro ◽  
Todd D Johnson ◽  
Karen L Christman ◽  
Michael E Davis

Introduction: Cell therapies have grown in popularity for myocardial regeneration post-infarction, but still suffer from poor retention, maturation and integration of delivered cells. Mechanical strain has been shown to alter cell size, shape, adherence and gene expression in cardiac cells. As a more recently identified cell type, the effect of mechanical strain on cardiac progenitor cells (CPCs) is unknown. This work aims to elucidate the role mechanical strain plays in CPC phenotype and if this response is matrix protein specific. We hypothesize that mechanical strain will improve CPC alignment and potential for connectivity. Methods: To examine the role of mechanical strain on CPCs, CPCs were seeded on FlexCell plates in the presence of a naturally-derived cardiac extracellularmatrix (cECM), collagen I (COL) or no protein (TCP) and strained 0% (static) or 10% at 1 Hz for 24 hours in a BioFlex system. CPC elongation, alignment, and size were evaluated by rhodamine-phalloidin staining. Connexin-43 expression was measured by Western and normalized to GAPDH. Data were analyzed by two-way ANOVA and Bonferroni post-test. Results: CPC area, independent of culture conditions, was 1020 ± 40 um2, corresponding to neonatal cardiomyocyte area. The aspect ratio (major/minor axis) of CPCs showed a trend for increased elongation with strain at (e.x. 2.0±0.2 for unstrained cECM compared to 2.7±0.1 for strained cECM; n=4, p>0.05). Static culture conditions, independent of matrix coating, showed 20±3% alignment of CPCs. Under strain, alignment increased to 30±2% on COL (n=4; p>0.05 for strained COL verus static COL) and 48±8% on cECM (n=4; p< 0.01 for strained cECM versus strained COL and p<0.001 for strained cECM verus static cECM). A fold change >2 for connexin-43 protein in strained versus static conditions, independent of matrix, was observed (n=2, p>0.05) and confirmed by immunocytochemistry. Conclusion: This work suggests that mechanical strain alters CPC phenotype. Increased strain-induced alignment appears to be matrix dependent. In conclusion, these studies provide insight into the role of both mechanical forces and biochemical responses in the function of CPCs; which could lead to improved outcomes following cellular transplantation.


Author(s):  
WILFREDO OLIVA-OLIVERA ◽  
LETICIA COÍN-Aragüez ◽  
SAID LHAMYANI ◽  
MERCEDES CLEMENTE-POSTIGO ◽  
JUAN ALCAIDE TORRES ◽  
...  

2020 ◽  
Vol 530 (1) ◽  
pp. 189-195
Author(s):  
Yubei Qu ◽  
Lin Zhang ◽  
Daikun He ◽  
Ning Xu ◽  
Yuedong Tang ◽  
...  

QJM ◽  
2018 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
W Baher ◽  
A A Abo Zeid ◽  
B Mohamed Fahmy ◽  
A Mohamed Hashem ◽  
R Ashraf Sakr ◽  
...  

Author(s):  
Min Yin ◽  
Yan Zhang ◽  
Haibo Yu ◽  
Xia Li

The regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs) have laid a sound foundation for their clinical application in various diseases. However, the clinical efficiency of MSC treatments varies depending on certain cell characteristics. Among these, the roles of cell aging or senescence cannot be excluded. Despite their stemness, evidence of senescence in MSCs has recently gained attention. Many factors may contribute to the senescence of MSCs, including MSC origin (biological niche), donor conditions (age, obesity, diseases, or unknown factors), and culture conditions in vitro. With the rapidly increasing prevalence of diabetes mellitus (DM) and gestational diabetes mellitus (GDM), the effects of hyperglycemia on the senescence of MSCs should be evaluated to improve the application of autologous MSCs. This review aims to present the available data on the senescence of MSCs, its relationship with hyperglycemia, and the strategies to suppress the senescence of MSCs in a hyperglycemic environment.


Oncotarget ◽  
2015 ◽  
Vol 6 (29) ◽  
pp. 26804-26813 ◽  
Author(s):  
Claudia Compagnucci ◽  
Stefania Petrini ◽  
Norimichi Higuraschi ◽  
Marina Trivisano ◽  
Nicola Specchio ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
X. Ambriz ◽  
P. de Lanerolle ◽  
J. R. Ambrosio

An understanding of the cytoskeleton’s importance in stem cells is essential for their manipulation and further clinical application. The cytoskeleton is crucial in stem cell biology and depends on physical and chemicals signals to define its structure. Additionally, cell culture conditions will be important in the proper maintenance of stemness, lineage commitment, and differentiation. This review focuses on the following areas: the role of the actin cytoskeleton of stem cells during differentiation, the significance of cellular morphology, signaling pathways involved in cytoskeletal rearrangement in stem cells, and the mechanobiology and mechanotransduction processes implicated in the interactions of stem cells with different surfaces of biomaterials, such as nanotopography, which is a physical cue influencing the differentiation of stem cells. Also, cancer stem cells are included since it is necessary to understand the role of their mechanical properties to develop new strategies to treat cancer. In this context, to study the stem cells requires integrated disciplines, including molecular and cellular biology, chemistry, physics, and immunology, as well as mechanobiology. Finally, since one of the purposes of studying stem cells is for their application in regenerative medicine, the deepest understanding is necessary in order to establish safety protocols and effective cell-based therapies.


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