Human tissue-engineered skeletal muscle: a novel 3D in vitro model for drug disposition and toxicity after intramuscular injection
| Autor: | Lieselot Decroix, Pieter Annaert, Dacha Gholobova, Nico Callewaert, Lieven Thorrez, Melanie Gérard, Linda Desender |
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| Přispěvatelé: | Faculty of Physical Education and Physical Therapy, Human Physiology and Sports Physiotherapy Research Group, Physiotherapy, Human Physiology and Anatomy, Department of Bio-engineering Sciences |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Toxicity Tests/methods Drug-Related Side Effects and Adverse Reactions Myoblasts Skeletal Cell Culture Techniques lcsh:Medicine Myoblasts Skeletal/metabolism Injections Intramuscular Models Biological Article 03 medical and health sciences 3D cell culture Tissue engineering In vivo Toxicity Tests medicine Humans Tissue Engineering/methods Myocyte Muscle Skeletal lcsh:Science Multidisciplinary Tissue Engineering Chemistry lcsh:R Skeletal muscle food and beverages Extracellular Matrix/metabolism In vitro Extracellular Matrix Cell biology Drug-Related Side Effects and Adverse Reactions/metabolism 030104 developmental biology medicine.anatomical_structure Muscle Skeletal/cytology Cell culture Toxicity lcsh:Q |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-14 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-30123-3 |
| Popis: | The development of laboratory-grown tissues, referred to as organoids, bio-artificial tissue or tissue-engineered constructs, is clearly expanding. We describe for the first time how engineered human muscles can be applied as a pre- or non-clinical model for intramuscular drug injection to further decrease and complement the use of in vivo animal studies. The human bio-artificial muscle (BAM) is formed in a seven day tissue engineering procedure during which human myoblasts fuse and differentiate to aligned myofibers in an extracellular matrix. The dimensions of the BAM constructs allow for injection and follow-up during several days after injection. A stereotactic setup allows controllable injection at multiple sites in the BAM. We injected several compounds; a dye, a hydrolysable compound, a reducible substrate and a wasp venom toxin. Afterwards, direct reflux, release and metabolism were assessed in the BAM constructs in comparison to 2D cell culture and isolated human muscle strips. Spectrophotometry and luminescence allowed to measure the release of the injected compounds and their metabolites over time. A release profile over 40 hours was observed in the BAM model in contrast to 2D cell culture, showing the capacity of the BAM model to function as a drug depot. We also determined compound toxicity on the BAMs by measuring creatine kinase release in the medium, which increased with increasing toxic insult. Taken together, we show that the BAM is an injectable human 3D cell culture model that can be used to measure release and metabolism of injected compounds in vitro. |
| Databáze: | OpenAIRE |
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