Engineered Muscle: A Tool for Studying Muscle Physiology and Function
Engineered Muscle: A Tool for Studying Muscle Physiology and Function
Recent advances in skeletal muscle tissue engineering have resulted in an in vitro tissue model that can be used for studying the effects of genetic alterations, pharmacological interventions, and exercise on muscle physiology and function. Here, we present applications for this technology to further our understanding of the molecular mechanisms underlying skeletal muscle adaptation in response to exercise.
The effort to develop three-dimensional (3D) skeletal muscle in vitro has been driven by a wide variety of goals including the following: 1) generating a source of replacement muscle tissue for the surgical correction of injury or congenital deformity; 2) developing a motor to drive machinery including prosthetics; 3) engineering a source of meat, free from animal diseases such as bovine spongiform encephalopathy; 4) producing a system for localized delivery of peptide growth factors; or 5) generating a 3D, in vitro, model for studying cell signaling, muscle development, and muscle physiology and function in response to genetic alterations, pharmacological interventions, and exercise. Those goals that require a large functional mass are decades away because of limitations such as the lack of vascularization and the absence of quality interfaces between biological and artificial materials. However, using engineered muscle for peptide delivery or modeling muscle physiology and function are possible with current technologies because a small amount of tissue is sufficient for the experimental purpose (for more detailed discussion of engineering muscle for delivering proteins and growth factors, see the work of Vandenburg).
For tissue engineered muscle to function as an effective model for the study of muscle physiology and function, it needs to satisfy five criteria. First, there needs to be a fast, easy, and standardized technique for engineering muscle. Second, it needs to be possible to engineer the tissue from transformed skeletal muscle cells such as C2C12s to decrease the variability of primary cell isolation and to allow for stable mutations to be made for testing gene function. Third, the physiology and function of the tissue need to be readily testable. Fourth, the model needs to be able to reproduce the effects of exercise/developmental stimuli. Fifth, the model needs to use standard, easy to use, and relatively inexpensive machines so that neither the cost nor the complexity of the engineering prevent investigators from being able to use the system. We, and others, have made good progress on the first four criteria (detailed below) and are currently working on the fifth.
Recent advances in skeletal muscle tissue engineering have resulted in an in vitro tissue model that can be used for studying the effects of genetic alterations, pharmacological interventions, and exercise on muscle physiology and function. Here, we present applications for this technology to further our understanding of the molecular mechanisms underlying skeletal muscle adaptation in response to exercise.
The effort to develop three-dimensional (3D) skeletal muscle in vitro has been driven by a wide variety of goals including the following: 1) generating a source of replacement muscle tissue for the surgical correction of injury or congenital deformity; 2) developing a motor to drive machinery including prosthetics; 3) engineering a source of meat, free from animal diseases such as bovine spongiform encephalopathy; 4) producing a system for localized delivery of peptide growth factors; or 5) generating a 3D, in vitro, model for studying cell signaling, muscle development, and muscle physiology and function in response to genetic alterations, pharmacological interventions, and exercise. Those goals that require a large functional mass are decades away because of limitations such as the lack of vascularization and the absence of quality interfaces between biological and artificial materials. However, using engineered muscle for peptide delivery or modeling muscle physiology and function are possible with current technologies because a small amount of tissue is sufficient for the experimental purpose (for more detailed discussion of engineering muscle for delivering proteins and growth factors, see the work of Vandenburg).
For tissue engineered muscle to function as an effective model for the study of muscle physiology and function, it needs to satisfy five criteria. First, there needs to be a fast, easy, and standardized technique for engineering muscle. Second, it needs to be possible to engineer the tissue from transformed skeletal muscle cells such as C2C12s to decrease the variability of primary cell isolation and to allow for stable mutations to be made for testing gene function. Third, the physiology and function of the tissue need to be readily testable. Fourth, the model needs to be able to reproduce the effects of exercise/developmental stimuli. Fifth, the model needs to use standard, easy to use, and relatively inexpensive machines so that neither the cost nor the complexity of the engineering prevent investigators from being able to use the system. We, and others, have made good progress on the first four criteria (detailed below) and are currently working on the fifth.
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