Engineering the cellular mechanical microenvironment to regulate stem cell chondrogenesis: Insights from a microgel model

AbstractEndothelial cells (EC) in vivo are continuously exposed to a mechanical microenvironment from blood flow, and fluidic shear stress plays an important role in EC behavior. New approaches to generate physiologically and pathologically relevant pulsatile flows are needed to understand EC behavior under different shear stress regimes. Here, we demonstrate an adaptable pump (Adapt-Pump) platform for generating pulsatile flows via quantitative imaging of human pluripotent stem cell-derived cardiac spheroids (CS). Pulsatile flows generated from the Adapt-Pump system can recapitulate unique CS contraction characteristics, accurately model responses to clinically relevant drugs, and simulate CS contraction changes in response to fluidic mechanical stimulation. We discovered that ECs differentiated under a long QT syndrome derived pathological pulsatile flow exhibit abnormal EC monolayer organization. This Adapt-Pump platform provides a powerful tool for modeling the cardiovascular system and improving our understanding of EC behavior under different mechanical microenvironments.

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StemBond hydrogels control the mechanical microenvironment for pluripotent stem cells

Nature Communications ◽

10.1038/s41467-021-26236-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Céline Labouesse ◽

Bao Xiu Tan ◽

Chibeza C. Agley ◽

Moritz Hofer ◽

Alexander K. Winkel ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Fate ◽

Pluripotent Stem Cells ◽

Cell Function ◽

Cell Attachment ◽

Substrate Stiffness ◽

Cell Fate Specification ◽

Confounding Variable ◽

Mechanical Microenvironment

AbstractStudies of mechanical signalling are typically performed by comparing cells cultured on soft and stiff hydrogel-based substrates. However, it is challenging to independently and robustly control both substrate stiffness and extracellular matrix tethering to substrates, making matrix tethering a potentially confounding variable in mechanical signalling investigations. Moreover, unstable matrix tethering can lead to poor cell attachment and weak engagement of cell adhesions. To address this, we developed StemBond hydrogels, a hydrogel in which matrix tethering is robust and can be varied independently of stiffness. We validate StemBond hydrogels by showing that they provide an optimal system for culturing mouse and human pluripotent stem cells. We further show how soft StemBond hydrogels modulate stem cell function, partly through stiffness-sensitive ERK signalling. Our findings underline how substrate mechanics impact mechanosensitive signalling pathways regulating self-renewal and differentiation, indicating that optimising the complete mechanical microenvironment will offer greater control over stem cell fate specification.

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Modulating the Electrical and Mechanical Microenvironment to Guide Neuronal Stem Cell Differentiation

Advanced Science ◽

10.1002/advs.202002112 ◽

2021 ◽

Vol 8 (7) ◽

pp. 2002112

Author(s):

Byeongtaek Oh ◽

Yu‐Wei Wu ◽

Vishal Swaminathan ◽

Vivek Lam ◽

Jun Ding ◽

...

Keyword(s):

Stem Cell ◽

Cell Differentiation ◽

Stem Cell Differentiation ◽

Neuronal Stem Cell ◽

Mechanical Microenvironment

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Author response for "Inhibition of neural stem cell aging through the transient induction of reprogramming factors"

10.1002/cne.24967/v2/response1 ◽

2020 ◽

Author(s):

Min Ji Han ◽

Won Ji Lee ◽

Joonhyuk Choi ◽

Yean Ju Hong ◽

Sang Jun Uhm ◽

...

Keyword(s):

Stem Cell ◽

Neural Stem Cell ◽

Author Response ◽

Cell Aging ◽

Stem Cell Aging ◽

Reprogramming Factors

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Decision letter for "Inhibition of neural stem cell aging through the transient induction of reprogramming factors"

10.1002/cne.24967/v2/decision1 ◽

2020 ◽

Keyword(s):

Stem Cell ◽

Neural Stem Cell ◽

Cell Aging ◽

Stem Cell Aging ◽

Reprogramming Factors

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The Response of Testes Cells to Low Level, Single dose Helium Particle Irradiation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053929 ◽

1982 ◽

Vol 40 ◽

pp. 252-253

Author(s):

D.E. Philpott ◽

W. Sapp ◽

C. Williams ◽

J. Stevenson ◽

S. Black ◽

...

Keyword(s):

Stem Cell ◽

Single Dose ◽

B Cell ◽

Cell Survival ◽

Spermatogonial Stem Cell ◽

Low Doses ◽

Particle Irradiation ◽

Stem Cell Survival ◽

Irradiation Injury ◽

Radio Sensitivity

Spermatogonial stem-cell survival after irradiation injury has been studied in rodents by histological counts of surviving cells. Many studies, including previous work from our laboratory, show that the spermatogonial population demonstrates a heterogeneous response to irradiation. The spermatogonia increase in radio-sensitivity as differentiation proceeds through the sequence As - Apr - A1 - A2 - A3 - A4 - In - B. The stem (As) cell is the most resistant and the B cell is the most sensitive. The purpose of this work is to investigate the response of spermatogonial cell to low doses (less than 10 0 rads) of helium particle irradiation.

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The Response of Testis Cells to Low Dose X-Irradiation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100099155 ◽

1981 ◽

Vol 39 ◽

pp. 542-543

Author(s):

D. E. Philpott ◽

W. Sapp ◽

C. Williams ◽

Joann Stevenson ◽

S. Black

Keyword(s):

Electron Microscopy ◽

Stem Cell ◽

Light Microscopy ◽

Dose Level ◽

Cross Sections ◽

Low Dose ◽

Light And Electron Microscopy ◽

Cellular Responses ◽

Post Irradiation ◽

X Irradiation

The response of spermatogonial cells to X-irradiation is well documented. It has been shown that there is a radiation resistent stem cell (As) which, after irradiation, replenishes the seminiferous epithelium. Most investigations in this area have dealt with radiation dosages of 100R or more. This study was undertaken to observe cellular responses at doses less than 100R of X-irradiation utilizing a system in which the tissue can be used for light and electron microscopy.Brown B6D2F1 mice aged 16 weeks were exposed to X-irradiation (225KeV; 15mA; filter 0.35 Cu; 50-60 R/min). Four mice were irradiated at each dose level between 1 and 100 rads. Testes were removed 3 days post-irradiation, fixed, and embedded. Sections were cut at 2 microns for light microscopy. After staining, surviving spermatogonia were identified and counted in tubule cross sections. The surviving fraction of spermatogonia compared to control, S/S0, was plotted against dose to give the curve shown in Fig. 1.

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The early development of antenna and antennal sensilla in the noctuid moth, Agrotis segetum (Insecta: Lepidoptera)

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100160066 ◽

1990 ◽

Vol 48 (3) ◽

pp. 502-503

Author(s):

Eric Hallberg ◽

Lina Hansén

Keyword(s):

Cell Death ◽

Stem Cell ◽

Early Development ◽

Larval Stage ◽

Pupal Stage ◽

Agrotis Segetum ◽

Antennal Sensilla ◽

Noctuid Moth ◽

Standard Procedures

The antennal rudiments in lepidopterous insects are present as disks during the larval stage. The tubular double-walled antennal disk is present beneath the larval antenna, and its inner layer gives rise to the adult antenna during the pupal stage. The sensilla develop from a cluster of cells that are derived from one stem cell, which gives rise to both sensory and enveloping cells. During the morphogenesis of the sensillum these cells undergo major transformations, including cell death. In the moth Agrotis segetum the pupal stage lasts about 14 days (temperature, 25°C). The antennae, clearly seen from the exterior, were dissected and fixed according to standard procedures (3 % glutaraldehyde in 0.15 M cacaodylate buffer, followed by 1 % osmiumtetroxide in the same buffer). Pupae from day 1 to day 8, of both sexes were studied.

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