Engineering of thick human functional myocardium via static stretching and electrical stimulation

Pretorius, Daniëlle; Kahn-Krell, Asher; LaBarge, Wesley; Lou, Xi; Zhang, Jianyi

doi:10.1016/j.isci.2022.103824

Cited by 9 publications

(12 citation statements)

References 57 publications

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“…Pretorius et al cultured engineered cardiac-muscle patches (> 2.1 mm thickness) from hiPSC-CMs in fibrin matrix and performed electromechanical conditioning for 10 days (i.e., static stretch + 2 Hz electrical stimulation of 15 or 22 V). The results of this study indicated a significant enhancement in structural aspects of CM maturation as shown by TEM and enhanced mRNA/protein levels of maturation genes in cardiac tissues subjected to a combination of static stretch + 20 V electrical stimulation ( 146 ).…”

Section: Engineered Heart Tissuementioning

confidence: 78%

Using human induced pluripotent stem cell-derived cardiomyocytes to understand the mechanisms driving cardiomyocyte maturation

Hamledari

Asghari

Jayousi

et al. 2022

Front. Cardiovasc. Med.

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Cardiovascular diseases are the leading cause of mortality and reduced quality of life globally. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide a personalized platform to study inherited heart diseases, drug-induced cardiac toxicity, and cardiac regenerative therapy. However, the immaturity of CMs obtained by current strategies is a major hurdle in utilizing hiPSC-CMs at their fullest potential. Here, the major findings and limitations of current maturation methodologies to enhance the utility of hiPSC-CMs in the battle against a major source of morbidity and mortality are reviewed. The most recent knowledge of the potential signaling pathways involved in the transition of fetal to adult CMs are assimilated. In particular, we take a deeper look on role of nutrient sensing signaling pathways and the potential role of cap-independent translation mediated by the modulation of mTOR pathway in the regulation of cardiac gap junctions and other yet to be identified aspects of CM maturation. Moreover, a relatively unexplored perspective on how our knowledge on the effects of preterm birth on cardiovascular development can be actually utilized to enhance the current understanding of CM maturation is examined. Furthermore, the interaction between the evolving neonatal human heart and brown adipose tissue as the major source of neonatal thermogenesis and its endocrine function on CM development is another discussed topic which is worthy of future investigation. Finally, the current knowledge regarding transcriptional mediators of CM maturation is still limited. The recent studies have produced the groundwork to better understand CM maturation in terms of providing some of the key factors involved in maturation and development of metrics for assessment of maturation which proves essential for future studies on in vitro PSC-CMs maturation.

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Section: Engineered Heart Tissuementioning

confidence: 78%

Using human induced pluripotent stem cell-derived cardiomyocytes to understand the mechanisms driving cardiomyocyte maturation

Hamledari

Asghari

Jayousi

et al. 2022

Front. Cardiovasc. Med.

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“…Therefore, increase in serial sarcomeres allows all the sarcomeres to be at their best or optimal length to produce force on a specific muscle excursion. The combined intervention of static stretching and NMES in the human myocardium showed an increase in the development of new Z lines and ‘gap junctions’, and sarcomere length (Pretorius et al, 2022). The current study supports the effects of NMES applied under stretching with sarcomere number as in the above‐mentioned studies.…”

Section: Discussionmentioning

confidence: 99%

The effect of neuromuscular electrical stimulation applied at different muscle lengths on muscle architecture and sarcomere morphology in rats

Uçar

Öner

Kuş

et al. 2023

The Anatomical Record

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Neuromuscular electrical stimulation (NMES) is often used to increase muscle strength and functionality. Muscle architecture is important for the skeletal muscle functionality. The aim of this study was to investigate the effects of NMES applied at different muscle lengths on skeletal muscle architecture. Twenty‐four rats were randomly assigned to four groups (two NMES groups and two control groups). NMES was applied on the extensor digitorum longus muscle at long muscle length, which is the longest and stretched position of the muscle at 170° plantar flexion, and at medium muscle length, which is the length of the muscle at 90° plantar flexion. A control group was created for each NMES group. NMES was applied for 8 weeks, 10 min/day, 3 days/week. After 8 weeks, muscle samples were removed at the NMES intervention lengths and examined macroscopically, and microscopically using a transmission electron microscope and streo‐microscope. Muscle damage, and architectural properties of the muscle including pennation angle, fibre length, muscle length, muscle mass, physiological cross‐sectional area, fibre length/muscle length, sarcomere length, sarcomere number were then evaluated. There was an increase in fibre length and sarcomere number, and a decrease in pennation angle at both lengths. In the long muscle length group, muscle length was increased, but widespread muscle damage was observed. These results suggest that the intervention of NMES at long muscle length can increase the muscle length but also causes muscle damage. In addition, the greater longitudinal increase in muscle length may be a result of the continuous degeneration‐regeneration cycle.

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“…The voltage amplitude is another major variant that needs to be balanced case-to-case depending on for instance electrode materials, distance between electrodes and the pulse width ( Björninen et al, 2018 ). Pretorius et al compared low voltage (15 V) and high voltage (22 V) stimulation on hiPSC-CM with the commonly used C-Pace (IonOptix) stimulator ( Pretorius et al, 2022 ). Cell constructs were manufactured into triple-layered cardiomyocyte patches and 2 ms voltage pulses at 2 Hz was applied for the patches under static stretching.…”

Section: Physical Stimulation and Supporting Matrixmentioning

confidence: 99%

Building blocks of microphysiological system to model physiology and pathophysiology of human heart

et al. 2023

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Microphysiological systems (MPS) are drawing increasing interest from academia and from biomedical industry due to their improved capability to capture human physiology. MPS offer an advanced in vitro platform that can be used to study human organ and tissue level functions in health and in diseased states more accurately than traditional single cell cultures or even animal models. Key features in MPS include microenvironmental control and monitoring as well as high biological complexity of the target tissue. To reach these qualities, cross-disciplinary collaboration from multiple fields of science is required to build MPS. Here, we review different areas of expertise and describe essential building blocks of heart MPS including relevant cardiac cell types, supporting matrix, mechanical stimulation, functional measurements, and computational modelling. The review presents current methods in cardiac MPS and provides insights for future MPS development with improved recapitulation of human physiology.

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Engineering of thick human functional myocardium via static stretching and electrical stimulation

Cited by 9 publications

References 57 publications

Using human induced pluripotent stem cell-derived cardiomyocytes to understand the mechanisms driving cardiomyocyte maturation

Using human induced pluripotent stem cell-derived cardiomyocytes to understand the mechanisms driving cardiomyocyte maturation

The effect of neuromuscular electrical stimulation applied at different muscle lengths on muscle architecture and sarcomere morphology in rats

Building blocks of microphysiological system to model physiology and pathophysiology of human heart

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