Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs

Madden, Lauran; Juhas, Mark; Kraus, William E.; Truskey, George A.; Bursac, Nenad

doi:10.7554/elife.04885

Cited by 289 publications

(434 citation statements)

References 45 publications

(83 reference statements)

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“…The μMACs contained densely packed and aligned myofibers parallel to the direction of the applied strain (Figures 5a-c), an important Magnetically actuated cell-laden microscale hydrogels Y Li et al indicator of maturation. 40 Structural maturation of myofibers over time was also evident from the progressive increase in myofiber diameter (from 16.5 ± 1.7 μm after 1 week of culture to 48.8 ± 9.8 μm after 4 weeks of culture) (Figure 5d) and from the expression of muscle-specific proteins including sarcomeric α-actinin (SAA) and MyHC ( Figure 5e and Supplementary Figure S11). Maturation of myotubes was also evident from confocal fluorescence images of transverse cross-sections of μMACs, which showed striated patterns of SAA and uniformly distributed MyHC.…”

Section: Resultsmentioning

confidence: 98%

Magnetically actuated cell-laden microscale hydrogels for probing strain-induced cell responses in three dimensions

Huang

Gao

et al. 2016

NPG Asia Mater

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Living cells respond to their mechanical microenvironments during development, healing, tissue remodeling and homeostasis attainment. However, this mechanosensitivity has not yet been established definitively for cells in three-dimensional (3D) culture environments, in part because of challenges associated with providing uniform and consistent 3D environments that can deliver a large range of physiological and pathophysiological strains to cells. Here, we report microscale magnetically actuated, cell-laden hydrogels (μMACs) for investigating the strain-induced cell response in 3D cultures. μMACs provide high-throughput arrays of defined 3D cellular microenvironments that undergo reversible, relatively homogeneous deformation following non-contact actuation under external magnetic fields. We present a technique that not only enables the application of these high strains (60%) to cells but also enables simplified microscopy of these specimens under tension. We apply the technique to reveal cellular strain-threshold and saturation behaviors that are substantially different from their 2D analogs, including spreading, proliferation, and differentiation. μMACs offer insights for mechanotransduction and may also provide a view of how cells respond to the extracellular matrix in a 3D manner.

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Section: Resultsmentioning

confidence: 98%

Magnetically actuated cell-laden microscale hydrogels for probing strain-induced cell responses in three dimensions

Huang

Gao

et al. 2016

NPG Asia Mater

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“…However, evidence showed that these myofibres failed to contract in response to electrical stimulation in the case of collagen-I hydrogels [40,42]. On the other hand, regarding fibrin-based hydrogels, a number of studies have established that this material is one of the best choices currently for engineering 3D muscle from mouse muscle cells [43,61,62].…”

Section: Hydrogels For In Vitro Engineering Skeletal Muscle Tissuesmentioning

confidence: 99%

“…Madden and co-workers [61] were the first to report a 3D culture model of human skeletal muscle that responds to electrical and biochemical stimulation in a manner similar to native skeletal muscle. This model was developed by culturing human myogenic cells expressing a GCaMP6 genetically encoded calcium indicator, within a supporting matrix composed of fibrin gel and matrigel.…”

Section: Drug Screeningmentioning

confidence: 99%

Hydrogel biomaterials and their therapeutic potential for muscle injuries and muscular dystrophies

Lev¹,

Seliktar²

2018

J. R. Soc. Interface.

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Muscular diseases such as muscular dystrophies and muscle injuries constitute a large group of ailments that manifest as muscle weakness, atrophy or fibrosis. Although cell therapy is a promising treatment option, the delivery and retention of cells in the muscle is difficult and prevents sustained regeneration needed for adequate functional improvements. Various types of biomaterials with different physical and chemical properties have been developed to improve the delivery of cells and/or growth factors for treating muscle injuries. Hydrogels are a family of materials with distinct advantages for use as cell delivery systems in muscle injuries and ailments, including their mild processing conditions, their similarities to natural tissue extracellular matrix, and their ability to be delivered with less invasive approaches. Moreover, hydrogels can be made to completely degrade in the body, leaving behind their biological payload in a process that can enhance the therapeutic process. For these reasons, hydrogels have shown great potential as cell delivery matrices. This paper reviews a few of the hydrogel systems currently being applied together with cell therapy and/or growth factor delivery to promote the therapeutic repair of muscle injuries and muscle wasting diseases such as muscular dystrophies.

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“…A recent preliminary success in producing bioengineered human myobundles with three-dimensional structure and effective contractility may be an important step towards translation into improved muscle mass and function in patients [13]. However, in order to generate fully functioning human myobundles we will need to resolve the problems of delivering sufficient oxygen by capillary networks, regulating fibre-type composition and providing adequate electrical and mechanical activation.…”

Section: Focusing On Muscle Mass and Sarcopeniamentioning

confidence: 99%

Future of muscle research in diabetes: a look into the crystal ball

Roden

2015

Diabetologia

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In type 2 diabetes, skeletal muscle is not only responsible for early metabolic abnormalities, but its contractile activity also offers an efficient prevention and treatment strategy. This outlook into the coming decades summarises challenges and opportunities for translational research on skeletal muscle in diabetes and related diseases. Currently, our understanding of the interactions between myocellular networks, the master regulators of resting metabolism, and muscle's position within multi-organ crosstalk, is incomplete. In the face of an ageing population, changes within muscle tissue appear to be the predominant mechanisms responsible for sarcopenia, but the relative roles of obesity and ageing as driving forces of its development are less clear. To address these research questions, innovative approaches to optimising exercise training or minimising sedentarism will need to be devised and tested in large-scale standardised prospective studies. Finally, another major challenge will be the identification and evaluation of muscle targets to prevent and treat metabolic diseases. This is one of a series of commentaries under the banner '50 years forward', giving personal opinions on future perspectives in diabetes, to celebrate the 50th anniversary of Diabetologia (1965Diabetologia ( -2015.

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Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs

Cited by 289 publications

References 45 publications

Magnetically actuated cell-laden microscale hydrogels for probing strain-induced cell responses in three dimensions

Magnetically actuated cell-laden microscale hydrogels for probing strain-induced cell responses in three dimensions

Hydrogel biomaterials and their therapeutic potential for muscle injuries and muscular dystrophies

Future of muscle research in diabetes: a look into the crystal ball

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