Metabolic reprogramming via mitochondrial delivery for enhanced maturation of chemically induced cardiomyocyte‐like cells
Abstract Heart degenerative diseases pose a significant challenge due to the limited ability of native heart to restore lost cardiomyocytes. Direct cellular reprogramming technology, particularly the use of small molecules, has emerged as a promising solution to prepare functional cardiomyocyte thro...
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| Format: | Article |
| Language: | English |
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Wiley
2024-12-01
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| Series: | MedComm |
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| Online Access: | https://doi.org/10.1002/mco2.70005 |
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| author | Yena Nam Yoonji Song Seung Ju Seo Ga Ryang Ko Seung Hyun Lee Eunju Cha Su Min Kwak Sumin Kim Mikyung Shin Yoonhee Jin Jung Seung Lee |
| author_facet | Yena Nam Yoonji Song Seung Ju Seo Ga Ryang Ko Seung Hyun Lee Eunju Cha Su Min Kwak Sumin Kim Mikyung Shin Yoonhee Jin Jung Seung Lee |
| author_sort | Yena Nam |
| collection | DOAJ |
| description | Abstract Heart degenerative diseases pose a significant challenge due to the limited ability of native heart to restore lost cardiomyocytes. Direct cellular reprogramming technology, particularly the use of small molecules, has emerged as a promising solution to prepare functional cardiomyocyte through faster and safer processes without genetic modification. However, current methods of direct reprogramming often exhibit low conversion efficiencies and immature characteristics of the generated cardiomyocytes, limiting their use in regenerative medicine. This study proposes the use of mitochondrial delivery to metabolically reprogram chemically induced cardiomyocyte‐like cells (CiCMs), fostering enhanced maturity and functionality. Our findings show that mitochondria sourced from high‐energy‐demand organs (liver, brain, and heart) can enhance structural maturation and metabolic functions. Notably, heart‐derived mitochondria resulted in CiCMs with a higher oxygen consumption rate capacity, enhanced electrical functionality, and higher sensitivity to hypoxic condition. These results are related to metabolic changes caused by increased number and size of mitochondria and activated mitochondrial fusion after mitochondrial treatment. In conclusion, our study suggests that mitochondrial delivery into CiCMs can be an effective strategy to promote cellular maturation, potentially contributing to the advancement of regenerative medicine and disease modeling. |
| format | Article |
| id | doaj-art-9ac65995c9ca41aab2584e07d9a0eb43 |
| institution | OA Journals |
| issn | 2688-2663 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj-art-9ac65995c9ca41aab2584e07d9a0eb432025-08-20T01:58:11ZengWileyMedComm2688-26632024-12-01512n/an/a10.1002/mco2.70005Metabolic reprogramming via mitochondrial delivery for enhanced maturation of chemically induced cardiomyocyte‐like cellsYena Nam0Yoonji Song1Seung Ju Seo2Ga Ryang Ko3Seung Hyun Lee4Eunju Cha5Su Min Kwak6Sumin Kim7Mikyung Shin8Yoonhee Jin9Jung Seung Lee10Department of Physiology Graduate School of Medical Science Brain Korea 21 Project Yonsei University College of Medicine Seoul Republic of KoreaDepartment of Biomedical Engineering Sungkyunkwan University (SKKU) Suwon Republic of KoreaDepartment of Physiology Graduate School of Medical Science Brain Korea 21 Project Yonsei University College of Medicine Seoul Republic of KoreaDepartment of Intelligent Precision Healthcare Convergence Sungkyunkwan University (SKKU) Suwon Republic of KoreaDepartment of Intelligent Precision Healthcare Convergence Sungkyunkwan University (SKKU) Suwon Republic of KoreaDepartment of Physiology Graduate School of Medical Science Brain Korea 21 Project Yonsei University College of Medicine Seoul Republic of KoreaDepartment of Medicine College of Medicine Yonsei University Graduate School Seoul Republic of KoreaDepartment of Intelligent Precision Healthcare Convergence Sungkyunkwan University (SKKU) Suwon Republic of KoreaDepartment of Biomedical Engineering Sungkyunkwan University (SKKU) Suwon Republic of KoreaDepartment of Physiology Graduate School of Medical Science Brain Korea 21 Project Yonsei University College of Medicine Seoul Republic of KoreaDepartment of Biomedical Engineering Sungkyunkwan University (SKKU) Suwon Republic of KoreaAbstract Heart degenerative diseases pose a significant challenge due to the limited ability of native heart to restore lost cardiomyocytes. Direct cellular reprogramming technology, particularly the use of small molecules, has emerged as a promising solution to prepare functional cardiomyocyte through faster and safer processes without genetic modification. However, current methods of direct reprogramming often exhibit low conversion efficiencies and immature characteristics of the generated cardiomyocytes, limiting their use in regenerative medicine. This study proposes the use of mitochondrial delivery to metabolically reprogram chemically induced cardiomyocyte‐like cells (CiCMs), fostering enhanced maturity and functionality. Our findings show that mitochondria sourced from high‐energy‐demand organs (liver, brain, and heart) can enhance structural maturation and metabolic functions. Notably, heart‐derived mitochondria resulted in CiCMs with a higher oxygen consumption rate capacity, enhanced electrical functionality, and higher sensitivity to hypoxic condition. These results are related to metabolic changes caused by increased number and size of mitochondria and activated mitochondrial fusion after mitochondrial treatment. In conclusion, our study suggests that mitochondrial delivery into CiCMs can be an effective strategy to promote cellular maturation, potentially contributing to the advancement of regenerative medicine and disease modeling.https://doi.org/10.1002/mco2.70005cardiomyocytescell reprogrammingmetabolic regulationmitochondrial transfer |
| spellingShingle | Yena Nam Yoonji Song Seung Ju Seo Ga Ryang Ko Seung Hyun Lee Eunju Cha Su Min Kwak Sumin Kim Mikyung Shin Yoonhee Jin Jung Seung Lee Metabolic reprogramming via mitochondrial delivery for enhanced maturation of chemically induced cardiomyocyte‐like cells MedComm cardiomyocytes cell reprogramming metabolic regulation mitochondrial transfer |
| title | Metabolic reprogramming via mitochondrial delivery for enhanced maturation of chemically induced cardiomyocyte‐like cells |
| title_full | Metabolic reprogramming via mitochondrial delivery for enhanced maturation of chemically induced cardiomyocyte‐like cells |
| title_fullStr | Metabolic reprogramming via mitochondrial delivery for enhanced maturation of chemically induced cardiomyocyte‐like cells |
| title_full_unstemmed | Metabolic reprogramming via mitochondrial delivery for enhanced maturation of chemically induced cardiomyocyte‐like cells |
| title_short | Metabolic reprogramming via mitochondrial delivery for enhanced maturation of chemically induced cardiomyocyte‐like cells |
| title_sort | metabolic reprogramming via mitochondrial delivery for enhanced maturation of chemically induced cardiomyocyte like cells |
| topic | cardiomyocytes cell reprogramming metabolic regulation mitochondrial transfer |
| url | https://doi.org/10.1002/mco2.70005 |
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