Engineered Early Embryonic Cardiac Tissue Increases Cardiomyocyte Proliferation by Cyclic Mechanical Stretch via p38-MAP Kinase Phosphorylation

Clause, Kelly C.; Tinney, Joseph P.; Liu, Li J.; Keller, Bradley B.; Tobita, Kimimasa

doi:10.1089/ten.tea.2008.0169

Cited by 35 publications

(48 citation statements)

References 52 publications

(33 reference statements)

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“…Previous studies have shown that cyclic mechanical stretch improves cardiomyocyte orientation 49 and proliferation, 50 and promotes hypertrophy. 51 Further, active forces between 0.05 and 2 mN have been previously reported after mechanical stimulation 52 ; Cx43 mRNA expression is increased threefold 49,53 and phosphorylated Akt expression increased 40% in mechanically stretched constructs when compared with static conditions.…”

Section: Fig 8 Growth Signaling Proteins (A)mentioning

confidence: 94%

Mimicking Isovolumic Contraction with Combined Electromechanical Stimulation Improves the Development of Engineered Cardiac Constructs

Morgan

Black²

2014

Tissue Engineering Part A

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Electrical and mechanical stimulation have both been used extensively to improve the function of cardiac engineered tissue as each of these stimuli is present in the physical environment during normal development in vivo. However, to date, there has been no direct comparison between electrical and mechanical stimulation and current published data are difficult to compare due to the different systems used to create the engineered cardiac tissue and the different measures of functionality studied as outcomes. The goals of this study were twofold. First, we sought to directly compare the effects of mechanical and electrical stimulation on engineered cardiac tissue. Second, we aimed to determine the importance of the timing of the two stimuli in relation to each other in combined electromechanical stimulation. We hypothesized that delaying electrical stimulation after the beginning of mechanical stimulation to mimic the biophysical environment present during isovolumic contraction would improve construct function by improving proteins responsible for cell-cell communication and contractility. To test this hypothesis, we created a bioreactor system that would allow us to electromechanically stimulate engineered tissue created from neonatal rat cardiac cells entrapped in fibrin gel during 2 weeks in culture. Contraction force was higher for all stimulation groups as compared with the static controls, with the delayed combined stimulation constructs having the highest forces. Mechanical stimulation alone displayed increased final cell numbers but there were no other differences between electrical and mechanical stimulation alone. Delayed combined stimulation resulted in an increase in SERCA2a and troponin T expression levels, which did not happen with synchronous combined stimulation, indicating that the timing of combined stimulation is important to maximize the beneficial effect. Increases in Akt protein expression levels suggest that the improvements are at least in part induced by hypertrophic growth. In summary, combined electromechanical stimulation can create engineered cardiac tissue with improved functional properties over electrical or mechanical stimulation alone, and the timing of the combined stimulation greatly influences its effects on engineered cardiac tissue.

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Section: Fig 8 Growth Signaling Proteins (A)mentioning

confidence: 94%

Mimicking Isovolumic Contraction with Combined Electromechanical Stimulation Improves the Development of Engineered Cardiac Constructs

Morgan

Black²

2014

Tissue Engineering Part A

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“…36 Using a similar system based on collagen and Matrigel, Clause et al generated engineered early embryonic cardiac tissue using embryonic cardiac cells from chicken. 37 They reported a 1.6-fold increase in active stress at L max following cyclic mechanical stretch stimulation for 48 h and concluded that contractile properties and cellular proliferative response to stretch mimic developing fetal myocardium.…”

Section: Kensah Et Almentioning

confidence: 98%

A Novel Miniaturized Multimodal Bioreactor for Continuous In Situ Assessment of Bioartificial Cardiac Tissue During Stimulation and Maturation

Kensah

Gruh

Viering

et al. 2011

Tissue Engineering Part C: Methods

103

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Stem cell-based cardiac tissue engineering is a promising approach for regenerative therapy of the injured heart. At present, the small number of stem cell-derived cardiomyocytes that can be obtained using current culture and enrichment techniques represents one of the key limitations for the development of functional bioartificial cardiac tissue (BCT). We have addressed this problem by construction of a novel bioreactor with functional features of larger systems that enables the generation and in situ monitoring of miniaturized BCTs. BCTs were generated from rat cardiomyocytes to demonstrate advantages and usefulness of the bioreactor. Tissues showed spontaneous, synchronized contractions with cell orientation along the axis of strain. Cyclic stretch induced cardiomyocyte hypertrophy, demonstrated by a shift of myosin heavy chain expression from the alpha to beta isoform, together with elevated levels of atrial natriuretic factor. Stretch led to a moderate increase in systolic force (1.42 AE 0.09 mN vs. 0.96 AE 0.09 mN in controls), with significantly higher forces observed after b-adrenergic stimulation with noradrenalin (2.54 AE 0.11 mN). Combined mechanical and b-adrenergic stimulation had no synergistic effect. This study demonstrates for the first time that mechanical stimulation and direct real-time contraction force measurement can be combined into a single multimodal bioreactor system, including electrical stimulation of excitable tissue, perfusion of the culture chamber, and the possibility of (fluorescence) microscopic assessment during continuous cultivation. Thus, this bioreactor represents a valuable tool for monitoring tissue development and, ultimately, the optimization of stem cell-based tissue replacement strategies in regenerative medicine.

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“…10-day cyclic mechanical stretch increased cardiomyocyte proliferation via p38 MAPK phosphorylation. 39 Shear stress induced proliferation of rat mesenchymal stem cells through pim-1 via ERK and p38 MAPK. 40 Oscillatory flow induces human osteoblast-like MG63 cell proliferation through activation of b3 and b1 integrins leading to the modulation of downstream ERK and Akt pathways.…”

Section: Stretch Increases Proliferation Without Differentiation In Dmentioning

confidence: 99%

Mechanical Stretch Increases the Proliferation While Inhibiting the Osteogenic Differentiation in Dental Pulp Stem Cells

Hara

Naruse

Ozawa

et al. 2013

Tissue Engineering Part A

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Dental pulp stem cells (DPSCs), which can differentiate into several types of cells, are subjected to mechanical stress by jaw movement and occlusal forces. In this study, we evaluated how the uniaxial mechanical stretch influences proliferation and differentiation of DPSCs. DPSCs were isolated and cultured from male SpragueDawley rats. Cultured DPSCs were identified by surface markers and the differentiation capabilities as adipocytes or osteoblasts. To examine the response to mechanical stress, uniaxial stretch was exposed to cultured DPSCs. We evaluated the impact of stretch on the intracellular signaling, proliferation, osteogenic differentiation, and gene expressions of DPSCs. Stretch increased the phosphorylation of Akt, ERK1/2, and p38 MAP kinase as well as the proliferation of DPSCs. The stretch-induced proliferation of DPSCs was abolished by the inhibition of the ERK pathway. On the other hand, stretch significantly decreased the osteogenic differentiation of DPSCs, but did not affect the adipogenic differentiation. We also confirmed mRNA expressions of osteocalcin and osteopontin were significantly suppressed by stretch. In conclusion, uniaxial stretch increased the proliferation of DPSCs, while suppressing osteogenic differentiation. These results suggest a crucial role of mechanical stretch in the preservation of DPSCs in dentin. Furthermore, mechanical stretch may be a useful tool for increasing the quantity of DPSCs in vitro for regenerative medicine.

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Engineered Early Embryonic Cardiac Tissue Increases Cardiomyocyte Proliferation by Cyclic Mechanical Stretch via p38-MAP Kinase Phosphorylation

Cited by 35 publications

References 52 publications

Mimicking Isovolumic Contraction with Combined Electromechanical Stimulation Improves the Development of Engineered Cardiac Constructs

Mimicking Isovolumic Contraction with Combined Electromechanical Stimulation Improves the Development of Engineered Cardiac Constructs

A Novel Miniaturized Multimodal Bioreactor for Continuous In Situ Assessment of Bioartificial Cardiac Tissue During Stimulation and Maturation

Mechanical Stretch Increases the Proliferation While Inhibiting the Osteogenic Differentiation in Dental Pulp Stem Cells

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