scholarly journals Mechanosensitive regulation of FGFR1 through the MRTF-SRF pathway

2019 ◽  
Author(s):  
Jip Zonderland ◽  
Silvia Rezzola ◽  
Lorenzo Moroni
Keyword(s):  
Tissue Engineering ◽  
Cancer Biology ◽  
Control Cell ◽  
Tissue Culture Plastic ◽  
Cancer Treatments ◽  
Differentiation Potential ◽  
Fgf Receptor ◽  
Proliferation And Differentiation ◽  
First Time ◽  
Fgfr1 Expression

AbstractControlling basic fibroblast growth factor (bFGF) signaling is important for both tissue-engineering purposes, controlling proliferation and differentiation potential, and for cancer biology, influencing tumor progression and metastasis. Here, we observed that human mesenchymal stromal cells (hMSCs) no longer responded to soluble or covalently bound bFGF when cultured on microfibrillar substrates, while fibroblasts did. This correlated with a downregulation of FGF receptor 1 (FGFR1) expression of hMSCs on microfibrillar substrates, compared to hMSCs on conventional tissue culture plastic (TCP). hMSCs also expressed less SRF on ESP scaffolds, compared to TCP, while fibroblasts maintained high FGFR1 and SRF expression. Inhibition of actin-myosin tension or the MRTF/SRF pathway decreased FGFR1 expression in hMSCs, fibroblasts and MG63 osteosarcoma cells. This downregulation was functional, as hMSCs became irresponsive to bFGF in the presence of MRTF/SRF inhibitor. Together, our data show that hMSCs, but not fibroblasts, are irresponsive to bFGF when cultured on microfibrillar susbtrates by downregulation of FGFR1 through the MRTF/SRF pathway. This is the first time FGFR1 expression has been shown to be mechanosensitive and adds to the sparse literature on FGFR1 regulation. These results could open up new targets for cancer treatments and could aid designing tissue engineering constructs that better control cell proliferation.

scholarly journals Actomyosin and the MRTF-SRF pathway downregulate FGFR1 in mesenchymal stromal cells

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Jip Zonderland ◽  
Silvia Rezzola ◽  
Lorenzo Moroni
Keyword(s):  
Cell Proliferation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Control Cell ◽  
Two Dimensions ◽  
Fgf Receptor ◽  
Human Mesenchymal Stromal Cells ◽  
Mg63 Cells ◽  
First Time ◽  
Fgfr1 Expression

Abstract Both biological and mechanical signals are known to influence cell proliferation. However, biological signals are mostly studied in two-dimensions (2D) and the interplay between these different pathways is largely unstudied. Here, we investigated the influence of the cell culture environment on the response to bFGF, a widely studied and important proliferation growth factor. We observed that human mesenchymal stromal cells (hMSCs), but not fibroblasts, lose the ability to respond to soluble or covalently bound bFGF when cultured on microfibrillar substrates. This behavior correlated with a downregulation of FGF receptor 1 (FGFR1) expression of hMSCs on microfibrillar substrates. Inhibition of actomyosin or the MRTF/SRF pathway decreased FGFR1 expression in hMSCs, fibroblasts and MG63 cells. To our knowledge, this is the first time FGFR1 expression is shown to be regulated through a mechanosensitive pathway in hMSCs. These results add to the sparse literature on FGFR1 regulation and potentially aid designing tissue engineering constructs that better control cell proliferation.

scholarly journals Bone Formation from Porcine Dental Germ Stem Cells on Surface Modified Polybutylene Succinate Scaffolds

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Nergis Abay ◽  
Gorke Gurel Pekozer ◽  
Mustafa Ramazanoglu ◽  
Gamze Torun Kose
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Cell Attachment ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Polybutylene Succinate ◽  
Tooth Germs ◽  
Surface Modified ◽  
First Time

Designing and providing a scaffold are very important for the cells in tissue engineering. Polybutylene succinate (PBS) has high potential as a scaffold for bone regeneration due to its capacity in cell proliferation and differentiation. Also, stem cells from 3rd molar tooth germs were favoured in this study due to their developmentally and replicatively immature nature. In this study, porcine dental germ stem cells (pDGSCs) seeded PBS scaffolds were used to investigate the effects of surface modification with fibronectin or laminin on these scaffolds to improve cell attachment, proliferation, and osteogenic differentiation for tissue engineering applications. The osteogenic potentials of pDGSCs on these modified and unmodified foams were examined to heal bone defects and the effects of fibronectin or laminin modified PBS scaffolds on pDGSC differentiation into bone were compared for the first time. For this study, MTS assay was used to assess the cytotoxic effects of modified and unmodified surfaces. For the characterization of pDGSCs, flow cytometry analysis was carried out. Besides, alkaline phosphatase (ALP) assay, von Kossa staining, real-time PCR, CM-Dil, and immunostaining were applied to analyze osteogenic potentials of pDGSCs. The results of these studies demonstrated that pDGSCs were differentiated into osteogenic cells on fibronectin modified PBS foams better than those on unmodified and laminin modified PBS foams.

scholarly journals Tailoring Nano-Porous Surface of Aligned Electrospun Poly (L-Lactic Acid) Fibers for Nerve Tissue Engineering

2021 ◽  
Vol 22 (7) ◽  
pp. 3536
Author(s):  
Hongyun Xuan ◽  
Biyun Li ◽  
Feng Xiong ◽  
Shuyuan Wu ◽  
Zhuojun Zhang ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Lactic Acid ◽  
Bacterial Adhesion ◽  
Bacterial Colonization ◽  
Cellular Responses ◽  
Surface Structures ◽  
Porous Surface ◽  
Nerve Tissue ◽  
Proliferation And Differentiation ◽  
Nerve Tissue Engineering

Despite the existence of many attempts at nerve tissue engineering, there is no ideal strategy to date for effectively treating defective peripheral nerve tissue. In the present study, well-aligned poly (L-lactic acid) (PLLA) nanofibers with varied nano-porous surface structures were designed within different ambient humidity levels using the stable jet electrospinning (SJES) technique. Nanofibers have the capacity to inhibit bacterial adhesion, especially with respect to Staphylococcus aureus (S. aureus). It was noteworthy to find that the large nano-porous fibers were less detrimentally affected by S. aureus than smaller fibers. Large nano-pores furthermore proved more conducive to the proliferation and differentiation of neural stem cells (NSCs), while small nano-pores were more beneficial to NSC migration. Thus, this study concluded that well-aligned fibers with varied nano-porous surface structures could reduce bacterial colonization and enhance cellular responses, which could be used as promising material in tissue engineering, especially for neuro-regeneration.

scholarly journals Fluid Flow Mechanical Stimulation-Assisted Cartridge Device for the Osteogenic Differentiation of Human Mesenchymal Stem Cells

Micromachines ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 927
Author(s):  
Ki-Taek Lim ◽  
Dinesh-K. Patel ◽  
Sayan-Deb Dutta ◽  
Keya Ganguly
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Fluid Flow ◽  
Osteogenic Differentiation ◽  
Flow Condition ◽  
Cultured Cells ◽  
Human Mesenchymal Stem Cells ◽  
Proliferation And Differentiation ◽  
Static Conditions

Human mesenchymal stem cells (hMSCs) have the potential to differentiate into different types of mesodermal tissues. In vitro proliferation and differentiation of hMSCs are necessary for bone regeneration in tissue engineering. The present study aimed to design and develop a fluid flow mechanically-assisted cartridge device to enhance the osteogenic differentiation of hMSCs. We used the fluorescence-activated cell-sorting method to analyze the multipotent properties of hMSCs and found that the cultured cells retained their stemness potential. We also evaluated the cell viabilities of the cultured cells via water-soluble tetrazolium salt 1 (WST-1) assay under different rates of flow (0.035, 0.21, and 0.35 mL/min) and static conditions and found that the cell growth rate was approximately 12% higher in the 0.035 mL/min flow condition than the other conditions. Moreover, the cultured cells were healthy and adhered properly to the culture substrate. Enhanced mineralization and alkaline phosphatase activity were also observed under different perfusion conditions compared to the static conditions, indicating that the applied conditions play important roles in the proliferation and differentiation of hMSCs. Furthermore, we determined the expression levels of osteogenesis-related genes, including the runt-related protein 2 (Runx2), collagen type I (Col1), osteopontin (OPN), and osteocalcin (OCN), under various perfusion vis-à-vis static conditions and found that they were significantly affected by the applied conditions. Furthermore, the fluorescence intensities of OCN and OPN osteogenic gene markers were found to be enhanced in the 0.035 mL/min flow condition compared to the control, indicating that it was a suitable condition for osteogenic differentiation. Taken together, the findings of this study reveal that the developed cartridge device promotes the proliferation and differentiation of hMSCs and can potentially be used in the field of tissue engineering.

scholarly journals The effects of locomotion on bone marrow mesenchymal stem cell fate: insight into mechanical regulation and bone formation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuanxiu Sun ◽  
Yu Yuan ◽  
Wei Wu ◽  
Le Lei ◽  
Lingli Zhang
Keyword(s):  
Bone Marrow ◽  
Cell Fate ◽  
Differentiation Potential ◽  
Stem Cell Fate ◽  
Proliferation And Differentiation ◽  
Marrow Mesenchymal Stem Cells ◽  
Adipocytic Differentiation ◽  
Regulatory Effects ◽  
Insight Into ◽  
Mechanical Regulation

AbstractBone marrow mesenchymal stem cells (BMSCs) refer to a heterogeneous population of cells with the capacity for self-renewal. BMSCs have multi-directional differentiation potential and can differentiate into chondrocytes, osteoblasts, and adipocytes under specific microenvironment or mechanical regulation. The activities of BMSCs are closely related to bone quality. Previous studies have shown that BMSCs and their lineage-differentiated progeny (for example, osteoblasts), and osteocytes are mechanosensitive in bone. Thus, a goal of this review is to discuss how these ubiquious signals arising from mechanical stimulation are perceived by BMSCs and then how the cells respond to them. Studies in recent years reported a significant effect of locomotion on the migration, proliferation and differentiation of BMSCs, thus, contributing to our bone mass. This regulation is realized by the various intersecting signaling pathways including RhoA/Rock, IFG, BMP and Wnt signalling. The mechanoresponse of BMSCs also provides guidance for maintaining bone health by taking appropriate exercises. This review will summarize the regulatory effects of locomotion/mechanical loading on BMSCs activities. Besides, a number of signalling pathways govern MSC fate towards osteogenic or adipocytic differentiation will be discussed. The understanding of mechanoresponse of BMSCs makes the foundation for translational medicine.

Application potential of three-dimensional silk fibroin scaffold using mesenchymal stem cells for cardiac regeneration

2021 ◽  
pp. 088532822110185
Author(s):  
Yuksel Cetin ◽  
Merve G Sahin ◽  
Fatma N Kok
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Silk Fibroin ◽  
Cardiac Tissue ◽  
Troponin I ◽  
Cardiac Tissue Engineering ◽  
Swelling Ratio ◽  
Differentiation Potential ◽  
Cardiomyogenic Differentiation

Cardiac tissue engineering focusing on biomaterial scaffolds incorporating cells from different sources has been explored to regenerate or repair damaged area as a lifesaving approach.The aim of this study was to evaluate the cardiomyocyte differentiation potential of human adipose mesenchymal stem cells (hAD-MSCs) as an alternative cell source on silk fibroin (SF) scaffolds for cardiac tissue engineering. The change in surface morphology of SF scaffolds depending on SF concentration (1–6%, w/v) and increase in their porosity upon application of unidirectional freezing were visualized by scanning electron microscopy (SEM). Swelling ratio was found to increase 2.4 fold when SF amount was decreased from 4% to 2%. To avoid excessive swelling, 4% SF scaffold with swelling ratio of 10% (w/w) was chosen for further studies.Biodegradation rate of SF scaffolds depended on enzymatic activity was found to be 75% weight loss of SF scaffolds at the day 14. The phenotype of hAD-MSCs and their multi-linage potential into chondrocytes, osteocytes, and adipocytes were shown by flow cytometry and immunohistochemical staining, respectively.The viability of hAD-MSCs on 3D SF scaffolds was determined as 90%, 118%, and 138% after 1, 7, and 14 days, respectively. The use of 3D SF scaffolds was associated with increased production of cardiomyogenic biomarkers: α-actinin, troponin I, connexin 43, and myosin heavy chain. The fabricated 3D SF scaffolds were proved to sustain hAD-MSCs proliferation and cardiomyogenic differentiation therefore, hAD-MSCs on 3D SF scaffolds may useful tool to regenerate or repair damaged area using cardiac tissue engineering techniques.

scholarly journals Molecular Imprinting Strategies for Tissue Engineering Applications: A Review

Polymers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 548
Author(s):  
Amedeo Franco Bonatti ◽  
Carmelo De Maria ◽  
Giovanni Vozzi
Keyword(s):  
Tissue Engineering ◽  
Molecularly Imprinted Polymers ◽  
Cell Interaction ◽  
Great Promise ◽  
Molecularly Imprinted ◽  
Proliferation And Differentiation ◽  
Promising Solution ◽  
Natural Tissue ◽  
A Current ◽  
Biophysical Cues

Tissue Engineering (TE) represents a promising solution to fabricate engineered constructs able to restore tissue damage after implantation. In the classic TE approach, biomaterials are used alongside growth factors to create a scaffolding structure that supports cells during the construct maturation. A current challenge in TE is the creation of engineered constructs able to mimic the complex microenvironment found in the natural tissue, so as to promote and guide cell migration, proliferation, and differentiation. In this context, the introduction inside the scaffold of molecularly imprinted polymers (MIPs)—synthetic receptors able to reversibly bind to biomolecules—holds great promise to enhance the scaffold-cell interaction. In this review, we analyze the main strategies that have been used for MIP design and fabrication with a particular focus on biomedical research. Furthermore, to highlight the potential of MIPs for scaffold-based TE, we present recent examples on how MIPs have been used in TE to introduce biophysical cues as well as for drug delivery and sequestering.

scholarly journals Comparison of proliferation and differentiation potential between mouse primary hepatocytes and embryonic hepatic progenitor cells in vitro

2013 ◽  
Vol 32 (2) ◽  
pp. 476-484 ◽  
Author(s):  
YUN HE ◽  
JIAN-WU ZHOU ◽  
LEI XU ◽  
MENG-JIA GONG ◽  
TONG-CHUAN HE ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Hepatic Progenitor Cells ◽  
Primary Hepatocytes ◽  
Differentiation Potential ◽  
Proliferation And Differentiation

Effect of pulsed electromagnetic field on the proliferation and differentiation potential of human bone marrow mesenchymal stem cells

2009 ◽  
Vol 30 (4) ◽  
pp. 251-260 ◽  
Author(s):  
Li-Yi Sun ◽  
Dean-Kuo Hsieh ◽  
Tzai-Chiu Yu ◽  
Hsien-Tai Chiu ◽  
Sheng-Fen Lu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Electromagnetic Field ◽  
Human Bone ◽  
Pulsed Electromagnetic Field ◽  
Differentiation Potential ◽  
Proliferation And Differentiation ◽  
Marrow Mesenchymal Stem Cells ◽  
Pulsed Electromagnetic
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