Integrin β1 activation by micro-scale curvature promotes pro-angiogenic secretion of human mesenchymal stem cells

2017 ◽  
Vol 5 (35) ◽  
pp. 7415-7425 ◽  
Author(s):  
Zhengdong Li ◽  
Weiwei Wang ◽  
Xun Xu ◽  
Karl Kratz ◽  
Jie Zou ◽  
...  

A cell culture substrate with micro-scale surface curvature promotes β1 integrin activation and pro-angiogenic secretion of mesenchymal stem cells.

Hepatology ◽  
2012 ◽  
Vol 56 (3) ◽  
pp. 1063-1073 ◽  
Author(s):  
Victoria Aldridge ◽  
Abhilok Garg ◽  
Nicholas Davies ◽  
David C. Bartlett ◽  
Janine Youster ◽  
...  

2014 ◽  
Vol 6 (18) ◽  
pp. 15686-15696 ◽  
Author(s):  
Ajay Tijore ◽  
Srivats Hariharan ◽  
Haiyang Yu ◽  
Chee Ren Ivan Lam ◽  
Feng Wen ◽  
...  

MRS Advances ◽  
2017 ◽  
Vol 2 (47) ◽  
pp. 2561-2570
Author(s):  
Xun Xu ◽  
Weiwei Wang ◽  
Zhengdong Li ◽  
Karl Kratz ◽  
Nan Ma ◽  
...  

ABSTRACTThe therapeutic effect of mesenchymal stem cells (MSCs) has been investigated in various clinical applications, in which their functional benefits are mainly attributed to the secretion of soluble factors. The enhancement of their therapeutic potential by physical and chemical properties of cell culture substrate is a safe and effective strategy, since they are highly sensitive to their microenvironment such as the elasticity and surface topography. In this study, we demonstrated that the geometry of polymeric substrate regulated the interleukin-6 (IL-6) secretion of human adipose derived MSCs. Polystyrene substrates comprising arrays of square-shaped (S50) or round-shaped (R50) microwells (side length or diameter of 50 μm and depth of 10 μm) were prepared by injection molding. Cellular apoptototic rate of MSCs was not affected by the microwell geometry, while the upregulated secretion of IL-6 and the enhancement of nuclear transcription factor STAT3 were detected in MSCs seeded on S50 substrate. The geometry-dependent modulatory effect was highly associated with ROCK signaling cascade. The inhibition of ROCK abolished the disparity in IL-6 secretion. These findings highlight the possibility to steer the secretion profile of stem cells via microwell geometry in combination with the manipulation of ROCK signaling pathway.


2019 ◽  
Vol 20 (21) ◽  
pp. 5467 ◽  
Author(s):  
Dalia Medhat ◽  
Clara I. Rodríguez ◽  
Arantza Infante

Mesenchymal stem cells (MSCs) are capable of differentiating into multilineage cells, thus making them a significant prospect as a cell source for regenerative therapy; however, the differentiation capacity of MSCs into osteoblasts seems to not be the main mechanism responsible for the benefits associated with human mesenchymal stem cells hMSCs when used in cell therapy approaches. The process of bone fracture restoration starts with an instant inflammatory reaction, as the innate immune system responds with cytokines that enhance and activate many cell types, including MSCs, at the site of the injury. In this review, we address the influence of MSCs on the immune system in fracture repair and osteogenesis. This paradigm offers a means of distinguishing target bone diseases to be treated with MSC therapy to enhance bone repair by targeting the crosstalk between MSCs and the immune system.


2020 ◽  
Vol 245 (7) ◽  
pp. 606-619
Author(s):  
Andrew Hamann ◽  
Alvin K Thomas ◽  
Tyler Kozisek ◽  
Eric Farris ◽  
Steffen Lück ◽  
...  

Nonviral gene delivery, though limited by inefficiency, has extensive utility in cell therapy, tissue engineering, and diagnostics. Substrate-mediated gene delivery (SMD) increases efficiency and allows transfection at a cell-biomaterial interface, by immobilizing and concentrating nucleic acid complexes on a surface. Efficient SMD generally requires substrates to be coated with serum or other protein coatings to mediate nucleic acid complex immobilization, as well as cell adhesion and growth; however, this strategy limits reproducibility and may be difficult to translate for clinical applications. As an alternative, we screened a chemically defined combinatorial library of 20 different extracellular matrix mimetic substrates containing combinations of (1) different sulfated polysaccharides that are essential extracellular matrix glycosaminoglycans (GAGs), with (2) mimetic peptides derived from adhesion proteins, growth factors, and cell-penetrating domains, for use as SMD coatings. We identified optimal substrates for DNA lipoplex and polyplex SMD transfection of fibroblasts and human mesenchymal stem cells. Optimal extracellular matrix mimetic substrates varied between cell type, donor source, and transfection reagent, but typically contained Heparin GAG and an adhesion peptide. Multiple substrates significantly increased transgene expression (i.e. 2- to 20-fold) over standard protein coatings. Considering previous research of similar ligands, we hypothesize extracellular matrix mimetic substrates modulate cell adhesion, proliferation, and survival, as well as plasmid internalization and trafficking. Our results demonstrate the utility of screening combinatorial extracellular matrix mimetic substrates for optimal SMD transfection towards application- and patient-specific technologies. Impact statement Substrate-mediated gene delivery (SMD) approaches have potential for modification of cells in applications where a cell-material interface exists. Conventional SMD uses ill-defined serum or protein coatings to facilitate immobilization of nucleic acid complexes, cell attachment, and subsequent transfection, which limits reproducibility and clinical utility. As an alternative, we screened a defined library of extracellular matrix mimetic substrates containing combinations of different glycosaminoglycans and bioactive peptides to identify optimal substrates for SMD transfection of fibroblasts and human mesenchymal stem cells. This strategy could be utilized to develop substrates for specific SMD applications in which variability exists between different cell types and patient samples.


2010 ◽  
Vol 30 (6) ◽  
pp. 455-455 ◽  
Author(s):  
Dongyan Shi ◽  
Dan Ma ◽  
Feiqing Dong ◽  
Chen Zong ◽  
Liyue Liu ◽  
...  

2012 ◽  
Vol 2 (1_suppl) ◽  
pp. s-0032-1320001-s-0032-1320001
Author(s):  
F. Mwale ◽  
H. T. Wang ◽  
L. Haglund ◽  
P. J. Roughley ◽  
J. Antoniou

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