Physiological and pharmacological stimulation for in vitro maturation of substrate metabolism in human induced pluripotent stem cell-derived cardiomyocytes
<div><p>Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enable human cardiac cells to be studied in vitro, although they use glucose as their primary metabolic substrate and do not recapitulate the properties of adult cardiomyocytes. Here, we have explored the inte...
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| مؤلفون آخرون: | , , , , , , , , , , , , |
| منشور في: |
2021
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| _version_ | 1864513516592955392 |
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| author | Colleen A. Lopez (18520071) |
| author2 | Heba Hussain A. A. Al-Siddiqi (18520074) Ujang Purnama (7427525) Sonia Iftekhar (18520077) Arne A. N. Bruyneel (8190483) Matthew Kerr (6822341) Rabia Nazir (13761940) Maria da Luz Sousa Fialho (18520080) Sophia Malandraki-Miller (18520083) Rita Alonaizan (18520086) Fatemeh Kermani (18520089) Lisa C. Heather (18520092) Jan Czernuszka (15305448) Carolyn A. Carr (7907915) |
| author2_role | author author author author author author author author author author author author author |
| author_facet | Colleen A. Lopez (18520071) Heba Hussain A. A. Al-Siddiqi (18520074) Ujang Purnama (7427525) Sonia Iftekhar (18520077) Arne A. N. Bruyneel (8190483) Matthew Kerr (6822341) Rabia Nazir (13761940) Maria da Luz Sousa Fialho (18520080) Sophia Malandraki-Miller (18520083) Rita Alonaizan (18520086) Fatemeh Kermani (18520089) Lisa C. Heather (18520092) Jan Czernuszka (15305448) Carolyn A. Carr (7907915) |
| author_role | author |
| dc.creator.none.fl_str_mv | Colleen A. Lopez (18520071) Heba Hussain A. A. Al-Siddiqi (18520074) Ujang Purnama (7427525) Sonia Iftekhar (18520077) Arne A. N. Bruyneel (8190483) Matthew Kerr (6822341) Rabia Nazir (13761940) Maria da Luz Sousa Fialho (18520080) Sophia Malandraki-Miller (18520083) Rita Alonaizan (18520086) Fatemeh Kermani (18520089) Lisa C. Heather (18520092) Jan Czernuszka (15305448) Carolyn A. Carr (7907915) |
| dc.date.none.fl_str_mv | 2021-04-08T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1038/s41598-021-87186-y |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Physiological_and_pharmacological_stimulation_for_in_vitro_maturation_of_substrate_metabolism_in_human_induced_pluripotent_stem_cell-derived_cardiomyocytes/25772007 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Cardiomyocytes Metabolic substrate Glucose metabolism Fatty acid oxidation (FAO) 3D culture |
| dc.title.none.fl_str_mv | Physiological and pharmacological stimulation for in vitro maturation of substrate metabolism in human induced pluripotent stem cell-derived cardiomyocytes |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <div><p>Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enable human cardiac cells to be studied in vitro, although they use glucose as their primary metabolic substrate and do not recapitulate the properties of adult cardiomyocytes. Here, we have explored the interplay between maturation by stimulation of fatty acid oxidation and by culture in 3D. We have investigated substrate metabolism in hiPSC-CMs grown as a monolayer and in 3D, in porous collagen-derived scaffolds and in engineered heart tissue (EHT), by measuring rates of glycolysis and glucose and fatty acid oxidation (FAO), and changes in gene expression and mitochondrial oxygen consumption. FAO was stimulated by activation of peroxisome proliferator-activated receptor alpha (PPARα), using oleate and the agonist WY-14643, which induced an increase in FAO in monolayer hiPSC-CMs. hiPSC-CMs grown in 3D on collagen-derived scaffolds showed reduced glycolysis and increased FAO compared with monolayer cells. Activation of PPARα further increased FAO in cells on collagen/elastin scaffolds but not collagen or collagen/chondroitin-4-sulphate scaffolds. In EHT, FAO was significantly higher than in monolayer cells or those on static scaffolds and could be further increased by culture with oleate and WY-14643. In conclusion, a more mature metabolic phenotype can be induced by culture in 3D and FAO can be incremented by pharmacological stimulation.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Scientific Reports<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-021-87186-y" target="_blank">https://dx.doi.org/10.1038/s41598-021-87186-y</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_6166c04850ac2c0bc759cc7f532ed443 |
| identifier_str_mv | 10.1038/s41598-021-87186-y |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25772007 |
| publishDate | 2021 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Physiological and pharmacological stimulation for in vitro maturation of substrate metabolism in human induced pluripotent stem cell-derived cardiomyocytesColleen A. Lopez (18520071)Heba Hussain A. A. Al-Siddiqi (18520074)Ujang Purnama (7427525)Sonia Iftekhar (18520077)Arne A. N. Bruyneel (8190483)Matthew Kerr (6822341)Rabia Nazir (13761940)Maria da Luz Sousa Fialho (18520080)Sophia Malandraki-Miller (18520083)Rita Alonaizan (18520086)Fatemeh Kermani (18520089)Lisa C. Heather (18520092)Jan Czernuszka (15305448)Carolyn A. Carr (7907915)Biological sciencesBiochemistry and cell biologyCardiomyocytesMetabolic substrateGlucose metabolismFatty acid oxidation (FAO)3D culture<div><p>Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enable human cardiac cells to be studied in vitro, although they use glucose as their primary metabolic substrate and do not recapitulate the properties of adult cardiomyocytes. Here, we have explored the interplay between maturation by stimulation of fatty acid oxidation and by culture in 3D. We have investigated substrate metabolism in hiPSC-CMs grown as a monolayer and in 3D, in porous collagen-derived scaffolds and in engineered heart tissue (EHT), by measuring rates of glycolysis and glucose and fatty acid oxidation (FAO), and changes in gene expression and mitochondrial oxygen consumption. FAO was stimulated by activation of peroxisome proliferator-activated receptor alpha (PPARα), using oleate and the agonist WY-14643, which induced an increase in FAO in monolayer hiPSC-CMs. hiPSC-CMs grown in 3D on collagen-derived scaffolds showed reduced glycolysis and increased FAO compared with monolayer cells. Activation of PPARα further increased FAO in cells on collagen/elastin scaffolds but not collagen or collagen/chondroitin-4-sulphate scaffolds. In EHT, FAO was significantly higher than in monolayer cells or those on static scaffolds and could be further increased by culture with oleate and WY-14643. In conclusion, a more mature metabolic phenotype can be induced by culture in 3D and FAO can be incremented by pharmacological stimulation.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Scientific Reports<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-021-87186-y" target="_blank">https://dx.doi.org/10.1038/s41598-021-87186-y</a></p>2021-04-08T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41598-021-87186-yhttps://figshare.com/articles/journal_contribution/Physiological_and_pharmacological_stimulation_for_in_vitro_maturation_of_substrate_metabolism_in_human_induced_pluripotent_stem_cell-derived_cardiomyocytes/25772007CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/257720072021-04-08T03:00:00Z |
| spellingShingle | Physiological and pharmacological stimulation for in vitro maturation of substrate metabolism in human induced pluripotent stem cell-derived cardiomyocytes Colleen A. Lopez (18520071) Biological sciences Biochemistry and cell biology Cardiomyocytes Metabolic substrate Glucose metabolism Fatty acid oxidation (FAO) 3D culture |
| status_str | publishedVersion |
| title | Physiological and pharmacological stimulation for in vitro maturation of substrate metabolism in human induced pluripotent stem cell-derived cardiomyocytes |
| title_full | Physiological and pharmacological stimulation for in vitro maturation of substrate metabolism in human induced pluripotent stem cell-derived cardiomyocytes |
| title_fullStr | Physiological and pharmacological stimulation for in vitro maturation of substrate metabolism in human induced pluripotent stem cell-derived cardiomyocytes |
| title_full_unstemmed | Physiological and pharmacological stimulation for in vitro maturation of substrate metabolism in human induced pluripotent stem cell-derived cardiomyocytes |
| title_short | Physiological and pharmacological stimulation for in vitro maturation of substrate metabolism in human induced pluripotent stem cell-derived cardiomyocytes |
| title_sort | Physiological and pharmacological stimulation for in vitro maturation of substrate metabolism in human induced pluripotent stem cell-derived cardiomyocytes |
| topic | Biological sciences Biochemistry and cell biology Cardiomyocytes Metabolic substrate Glucose metabolism Fatty acid oxidation (FAO) 3D culture |