Modeling the Effect of TNF-α upon Drug-Induced Toxicity in Human, Tissue-Engineered Myobundles
| Autor: | Christian A Boehm, William E. Kraus, Kim M. Huffman, Samantha L Lasater, George A. Truskey, Michaela J Walker, Danielle Dawes, Catherine E. Oliver, Michael M. Cunningham, Brittany N J Davis, Jeffrey W. Santoso |
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| Rok vydání: | 2019 |
| Předmět: |
Drug
media_common.quotation_subject Myoblasts Skeletal 0206 medical engineering Biomedical Engineering Inflammation 02 engineering and technology Pharmacology Models Biological Article Cachexia Cell Line Pathogenesis Mice medicine Animals Humans Doxorubicin Muscle Skeletal media_common Antibiotics Antineoplastic Tissue Engineering Tetanus business.industry Tumor Necrosis Factor-alpha Skeletal muscle medicine.disease 020601 biomedical engineering 3. Good health medicine.anatomical_structure Sarcopenia medicine.symptom business medicine.drug |
| Zdroj: | Ann Biomed Eng |
| ISSN: | 1573-9686 |
| Popis: | A number of significant muscle diseases, such as cachexia, sarcopenia, systemic chronic inflammation, along with inflammatory myopathies share TNF-α-dominated inflammation in their pathogenesis. In addition, inflammatory episodes may increase susceptibility to drug toxicity. To assess the effect of TNF-α-induced inflammation on drug responses, we engineered 3D, human skeletal myobundles, chronically exposed them to TNF-α during maturation, and measured the combined response of TNF-α and the chemotherapeutic doxorubicin on muscle function. First, the myobundle inflammatory environment was characterized by assessing the effects of TNF-α on 2D human skeletal muscle cultures and 3D human myobundles. High doses of TNF-α inhibited maturation in human 2D cultures and maturation and function in 3D myobundles. Then, a tetanus force dose–response curve was constructed to characterize doxorubicin’s effects on function alone. The combination of TNF-α and 10 nM doxorubicin exhibited a synergistic effect on both twitch and tetanus force production. Overall, the results demonstrated that inflammation of a 3D, human skeletal muscle inflammatory system alters the response to doxorubicin. |
| Databáze: | OpenAIRE |
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