scholarly journals The nuclear piston activates mechanosensitive ion channels to generate cell migration paths in confining microenvironments

2021 ◽  
Vol 7 (2) ◽  
pp. eabd4058
Author(s):  
Hong-pyo Lee ◽  
Farid Alisafaei ◽  
Kolade Adebawale ◽  
Julie Chang ◽  
Vivek B. Shenoy ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Migration ◽  
Ion Channels ◽  
Hydrostatic Pressure ◽  
Osmotic Pressure ◽  
Mechanosensitive Ion Channels ◽  
Modeling And Experiments ◽  
Opening Up ◽  
Over Time

Cell migration in confining microenvironments is limited by the ability of the stiff nucleus to deform through pores when migration paths are preexisting and elastic, but how cells generate these paths remains unclear. Here, we reveal a mechanism by which the nucleus mechanically generates migration paths for mesenchymal stem cells (MSCs) in confining microenvironments. MSCs migrate robustly in nanoporous, confining hydrogels that are viscoelastic and plastic but not in hydrogels that are more elastic. To migrate, MSCs first extend thin protrusions that widen over time because of a nuclear piston, thus opening up a migration path in a confining matrix. Theoretical modeling and experiments indicate that the nucleus pushing into the protrusion activates mechanosensitive ion channels, leading to an influx of ions that increases osmotic pressure, which outcompetes hydrostatic pressure to drive protrusion expansion. Thus, instead of limiting migration, the nucleus powers migration by generating migration paths.

Local calcium signalling is mediated by mechanosensitive ion channels in mesenchymal stem cells

2017 ◽  
Vol 482 (4) ◽  
pp. 563-568 ◽  
Author(s):  
Vladislav I. Chubinskiy-Nadezhdin ◽  
Valeria Y. Vasileva ◽  
Natalia A. Pugovkina ◽  
Irina O. Vassilieva ◽  
Elena A. Morachevskaya ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ion Channels ◽  
Calcium Signalling ◽  
Mechanosensitive Ion Channels

scholarly journals Effect of Scrapie Prion Infection in Ovine Bone Marrow-Derived Mesenchymal Stem Cells and Ovine Mesenchymal Stem Cell-Derived Neurons

Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1137
Author(s):  
Laura García-Mendívil ◽  
Diego R. Mediano ◽  
Adelaida Hernaiz ◽  
David Sanz-Rubio ◽  
Francisco J. Vázquez ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cellular Prion Protein ◽  
Transmissible Spongiform Encephalopathies ◽  
Post Inoculation ◽  
Spongiform Encephalopathies ◽  
Prion Infection ◽  
Over Time

Scrapie is a prion disease affecting sheep and goats and it is considered a prototype of transmissible spongiform encephalopathies (TSEs). Mesenchymal stem cells (MSCs) have been proposed as candidates for developing in vitro models of prion diseases. Murine MSCs are able to propagate prions after previous mouse-adaptation of prion strains and, although ovine MSCs express the cellular prion protein (PrPC), their susceptibility to prion infection has never been investigated. Here, we analyze the potential of ovine bone marrow-derived MSCs (oBM-MSCs), in growth and neurogenic conditions, to be infected by natural scrapie and propagate prion particles (PrPSc) in vitro, as well as the effect of this infection on cell viability and proliferation. Cultures were kept for 48–72 h in contact with homogenates of central nervous system (CNS) samples from scrapie or control sheep. In growth conditions, oBM-MSCs initially maintained detectable levels of PrPSc post-inoculation, as determined by Western blotting and ELISA. However, the PrPSc signal weakened and was lost over time. oBM-MSCs infected with scrapie displayed lower cell doubling and higher doubling times than those infected with control inocula. On the other hand, in neurogenic conditions, oBM-MSCs not only maintained detectable levels of PrPSc post-inoculation, as determined by ELISA, but this PrPSc signal also increased progressively over time. Finally, inoculation with CNS extracts seems to induce the proliferation of oBM-MSCs in both growth and neurogenic conditions. Our results suggest that oBM-MSCs respond to prion infection by decreasing their proliferation capacity and thus might not be permissive to prion replication, whereas ovine MSC-derived neuron-like cells seem to maintain and replicate PrPSc.

Hydrostatic Pressure Stimulation of Human Mesenchymal Stem Cells Seeded on Collagen-Based Artificial Extracellular Matrices

2009 ◽  
Vol 132 (2) ◽  
Author(s):  
Ricarda Hess ◽  
Timothy Douglas ◽  
Kenneth A. Myers ◽  
Barbe Rentsch ◽  
Claudia Rentsch ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Hydrostatic Pressure ◽  
Osteogenic Differentiation ◽  
Mechanical Stimulation ◽  
Human Mesenchymal Stem Cells ◽  
Extracellular Matrices ◽  
Mrna Levels ◽  
Alp Activity ◽  
Osteoblastic Phenotype

Human mesenchymal stem cells (hMSCs) from bone marrow are considered a promising cell source for bone tissue engineering applications because of their ability to differentiate into cells of the osteoblastic lineage. Mechanical stimulation is able to promote osteogenic differentiation of hMSC; however, the use of hydrostatic pressure (HP) has not been well studied. Artificial extracellular matrices containing collagen and chondroitin sulfate (CS) have promoted the expression of an osteoblastic phenotype by hMSCs. However, there has been little research into the combined effects of biochemical stimulation by matrices and simultaneous mechanical stimulation. In this study, artificial extracellular matrices generated from collagen and/or CS were coated onto polycaprolactone-co-lactide substrates, seeded with hMSCs and subjected to cyclic HP at various time points during 21 days after cell seeding to investigate the effects of biochemical, mechanical, and combined biochemical and mechanical stimulations. Cell differentiation was assessed by analyzing the expression of alkaline phosphatase (ALP) at the protein- and mRNA levels, as well as for calcium accumulation. The timing of HP stimulation affected hMSC proliferation and expression of ALP activity. HP stimulation after 6 days was most effective at promoting ALP activity. CS-containing matrices promoted the osteogenic differentiation of hMSCs. A combination of both CS-containing matrices and cyclic HP yields optimal effects on osteogenic differentiation of hMSCs on scaffolds compared with individual responses.

scholarly journals Reprint of: Mechanosensitive ion channels in cell migration

2021 ◽  
pp. 203730
Author(s):  
Brenda Canales Coutiño ◽  
Roberto Mayor
Keyword(s):  
Cell Migration ◽  
Ion Channels ◽  
Mechanosensitive Ion Channels

Abstract 47: Age of Donor of Human Mesenchymal Stem Cells Drastically Affects Structural and Functional Recovery After Cell Therapy Following Ischemic Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Susumu Yamaguchi ◽  
Nobutaka Horie ◽  
Katsuya Satoh ◽  
Yoichi Morofuji ◽  
Tsuyoshi Izumo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Migration ◽  
Ischemic Stroke ◽  
Functional Recovery ◽  
Human Mesenchymal Stem Cells ◽  
Trophic Factor ◽  
Donor Age ◽  
Vessel Maturation ◽  
Factor Secretion

Background and purpose: Cell transplantation therapy holds great potential to improve impairments after stroke. However, the importance of donor age on therapeutic efficacy is uncertain. We investigate regenerative capacity of transplanted cells focusing on donor age (young vs. old) for ischemic stroke. Methods: The value of platelet-derived growth factor (PDGF)-BB secreted from human mesenchymal stem cells (hMSC) was analyzed regarding in two age groups; young (20-30 years) and old (57-65 years) in vitro. Male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion, and received young or old hMSC trans-arterially at 24 h after stroke. Functional recovery was assessed with modified neurological severity score (mNSS). Structural recovery was assessed on neovascularization and endogenous cell migration as well as trophic factor secretion. Results: The value of PDGF-BB was significantly higher in young hMSC (40.47±4.29 pg/ml/10 4 cells) than that in old hMSC (25.35±3.16 pg/ml/10 4 cells; P =0.02) and negatively correlated with age ( P =0.048, r=-0.79, Spearman). Rats treated with young hMSC (3.7±0.6) showed better behavior recovery in mNSS with prevention of brain atrophy than that with control (6.1±0.5) or old (5.2±0.7) at D21 ( P <0.01). The number of RECA-1 and PDGFR-β double positive vessels in rat with young hMSC (113±48.6/mm 2 ) was higher than that in control (61.5±35.9/mm 2 ) or old (76.9±36.9/mm 2 ) suggesting vessel maturation ( P <0.01). Interestingly, migration of neural stem/progenitor cells expressing Musashi-1 positively correlated with astrocyte process alignment ( P <0.01, r=0.27; Spearman), which was more pronounced in young hMSC ( P <0.05). Conclusions: Aging of hMSC may be the critical factor which affects outcome of cell therapy, and transplantation of young hMSC could provide better functional recovery by vessel maturation and endogenous cell migration potentially due to dominance of trophic factor secretion.

scholarly journals BONE MARROW-DERIVED MESENCHYMAL STEM CELLS UPREGULATE ENDOMETRIAL STROMAL CELL MIGRATION BUT NOT PROLIFERATION

2020 ◽  
Vol 114 (3) ◽  
pp. e100
Author(s):  
Qingshi Zhao ◽  
Yahaira Naaldijk ◽  
Oleta A. Sandiford ◽  
Nicole M. Marchetto ◽  
Nataki C. Douglas ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cell Migration ◽  
Stromal Cell ◽  
Endometrial Stromal Cell
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