Matrigel 3D bioprinting of contractile human skeletal muscle models recapitulating exercise and pharmacological responses
| Autor: | Heidi Jeker, Martin W. Steinmann, Angela Alave Reyes-Furrer, Nathalie Accart, Dominic Bachmann, Hansjoerg Keller, Epifania Bono, Markus Rimann, Martin Rausch, Sonia De Andrade, Andrew Dunbar |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
QH301-705.5
Medicine (miscellaneous) Stimulation Drug development Biofabrication Article General Biochemistry Genetics and Molecular Biology law.invention Muscle hypertrophy Matrigel law Caffeine Precursor cell Myokine medicine Humans Biology (General) Muscle Skeletal Exercise Protein kinase B 610.28: Biomedizin Biomedizinische Technik 3D bioprinting Contraction business.industry Human skeletal muscle model Imidazoles Bioprinting Skeletal muscle Electric Stimulation Cell biology 3Rs principle Drug Combinations Hydrogel medicine.anatomical_structure Drug screening Pyrazines Alternative method Printing Three-Dimensional Musculoskeletal models Proteoglycans Collagen Laminin General Agricultural and Biological Sciences business Muscle Contraction |
| Zdroj: | Communications Biology, Vol 4, Iss 1, Pp 1-12 (2021) Communications Biology |
| Popis: | A key to enhance the low translatability of preclinical drug discovery are in vitro human three-dimensional (3D) microphysiological systems (MPS). Here, we show a new method for automated engineering of 3D human skeletal muscle models in microplates and functional compound screening to address the lack of muscle wasting disease medication. To this end, we adapted our recently described 24-well plate 3D bioprinting platform with a printhead cooling system to allow microvalve-based drop-on-demand printing of cell-laden Matrigel containing primary human muscle precursor cells. Mini skeletal muscle models develop within a week exhibiting contractile, striated myofibers aligned between two attachment posts. As an in vitro exercise model, repeated high impact stimulation of contractions for 3 h by a custom-made electrical pulse stimulation (EPS) system for 24-well plates induced interleukin-6 myokine expression and Akt hypertrophy pathway activation. Furthermore, the known muscle stimulators caffeine and Tirasemtiv acutely increase EPS-induced contractile force of the models. This validated new human muscle MPS will benefit development of drugs against muscle wasting diseases. Moreover, our Matrigel 3D bioprinting platform will allow engineering of non-self-organizing complex human 3D MPS. Alave-Furrer et al adapted their recently-developed 3D bioprinting platform to allow microvalve-based drop-on-demand printing of cell-laden Matrigel containing primary human muscle precursor cells. Their bioprinting platform recapitulated aspects of exercise and pharmacological responses and thus could aid the engineering of more complex 3D microphysiological systems. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|