Pluripotent stem cell-derived committed cardiac progenitors remuscularize damaged ischemic hearts and improve their function in pigs
Ischemic heart disease, which is often associated with irreversibly damaged heart muscle, is a major global health burden. Here, we report the potential of stem cell-derived committed cardiac progenitors (CCPs) have in regenerative cardiology. Human pluripotent embryonic stem cells were differentiat...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2023
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| Online Access: | https://hdl.handle.net/10356/169965 |
| _version_ | 1811690696926560256 |
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| author | Yap, Lynn Chong, Li Yen Tan, Clarissa Adusumalli, Swarnaseetha Seow, Millie Guo, Jing Cai, Zuhua Loo, Sze Jie Lim, Eric Tan, Ru San Grishina, Elina Soong, Poh Loong Lath, Narayan Ye, Lei Petretto, Enrico Tryggvason, Karl |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Yap, Lynn Chong, Li Yen Tan, Clarissa Adusumalli, Swarnaseetha Seow, Millie Guo, Jing Cai, Zuhua Loo, Sze Jie Lim, Eric Tan, Ru San Grishina, Elina Soong, Poh Loong Lath, Narayan Ye, Lei Petretto, Enrico Tryggvason, Karl |
| author_sort | Yap, Lynn |
| collection | NTU |
| description | Ischemic heart disease, which is often associated with irreversibly damaged heart muscle, is a major global health burden. Here, we report the potential of stem cell-derived committed cardiac progenitors (CCPs) have in regenerative cardiology. Human pluripotent embryonic stem cells were differentiated to CCPs on a laminin 521 + 221 matrix, characterized with bulk and single-cell RNA sequencing, and transplanted into infarcted pig hearts. CCPs differentiated for eleven days expressed a set of genes showing higher expression than cells differentiated for seven days. Functional heart studies revealed significant improvement in left ventricular ejection fraction at four and twelve weeks following transplantation. We also observed significant improvements in ventricular wall thickness and a reduction in infarction size after CCP transplantation (p-value < 0.05). Immunohistology analyses revealed in vivo maturation of the CCPs into cardiomyocytes (CM). We observed temporary episodes of ventricular tachyarrhythmia (VT) in four pigs and persistent VT in one pig, but the remaining five pigs exhibited normal sinus rhythm. Importantly, all pigs survived without the formation of any tumors or VT-related abnormalities. We conclude that pluripotent stem cell-derived CCPs constitute a promising possibility for myocardial infarction treatment and that they may positively impact regenerative cardiology. |
| first_indexed | 2024-10-01T06:08:06Z |
| format | Journal Article |
| id | ntu-10356/169965 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:08:06Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1699652023-08-20T15:37:34Z Pluripotent stem cell-derived committed cardiac progenitors remuscularize damaged ischemic hearts and improve their function in pigs Yap, Lynn Chong, Li Yen Tan, Clarissa Adusumalli, Swarnaseetha Seow, Millie Guo, Jing Cai, Zuhua Loo, Sze Jie Lim, Eric Tan, Ru San Grishina, Elina Soong, Poh Loong Lath, Narayan Ye, Lei Petretto, Enrico Tryggvason, Karl Lee Kong Chian School of Medicine (LKCMedicine) Duke-NUS Medical School Science::Medicine Cardiac Progenitors Heart Muscles Ischemic heart disease, which is often associated with irreversibly damaged heart muscle, is a major global health burden. Here, we report the potential of stem cell-derived committed cardiac progenitors (CCPs) have in regenerative cardiology. Human pluripotent embryonic stem cells were differentiated to CCPs on a laminin 521 + 221 matrix, characterized with bulk and single-cell RNA sequencing, and transplanted into infarcted pig hearts. CCPs differentiated for eleven days expressed a set of genes showing higher expression than cells differentiated for seven days. Functional heart studies revealed significant improvement in left ventricular ejection fraction at four and twelve weeks following transplantation. We also observed significant improvements in ventricular wall thickness and a reduction in infarction size after CCP transplantation (p-value < 0.05). Immunohistology analyses revealed in vivo maturation of the CCPs into cardiomyocytes (CM). We observed temporary episodes of ventricular tachyarrhythmia (VT) in four pigs and persistent VT in one pig, but the remaining five pigs exhibited normal sinus rhythm. Importantly, all pigs survived without the formation of any tumors or VT-related abnormalities. We conclude that pluripotent stem cell-derived CCPs constitute a promising possibility for myocardial infarction treatment and that they may positively impact regenerative cardiology. Published version This work has been supported by grants from the NMRC and NRF of Singapore (MOHSTaR18may-0001 and CRP24-2020-0083), Goh Cardiovascular Research (Duke NUS-GCR/2020/0018), Tanoto Foundation and a collaborative grant from Novo Nordisk A/S to K.T. 2023-08-16T07:52:16Z 2023-08-16T07:52:16Z 2023 Journal Article Yap, L., Chong, L. Y., Tan, C., Adusumalli, S., Seow, M., Guo, J., Cai, Z., Loo, S. J., Lim, E., Tan, R. S., Grishina, E., Soong, P. L., Lath, N., Ye, L., Petretto, E. & Tryggvason, K. (2023). Pluripotent stem cell-derived committed cardiac progenitors remuscularize damaged ischemic hearts and improve their function in pigs. NPJ Regenerative Medicine, 8(1), 26-. https://dx.doi.org/10.1038/s41536-023-00302-6 2057-3995 https://hdl.handle.net/10356/169965 10.1038/s41536-023-00302-6 37236990 2-s2.0-85160670463 1 8 26 en NPJ Regenerative Medicine © The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http:// creativecommons.org/licenses/by/4.0/. application/pdf |
| spellingShingle | Science::Medicine Cardiac Progenitors Heart Muscles Yap, Lynn Chong, Li Yen Tan, Clarissa Adusumalli, Swarnaseetha Seow, Millie Guo, Jing Cai, Zuhua Loo, Sze Jie Lim, Eric Tan, Ru San Grishina, Elina Soong, Poh Loong Lath, Narayan Ye, Lei Petretto, Enrico Tryggvason, Karl Pluripotent stem cell-derived committed cardiac progenitors remuscularize damaged ischemic hearts and improve their function in pigs |
| title | Pluripotent stem cell-derived committed cardiac progenitors remuscularize damaged ischemic hearts and improve their function in pigs |
| title_full | Pluripotent stem cell-derived committed cardiac progenitors remuscularize damaged ischemic hearts and improve their function in pigs |
| title_fullStr | Pluripotent stem cell-derived committed cardiac progenitors remuscularize damaged ischemic hearts and improve their function in pigs |
| title_full_unstemmed | Pluripotent stem cell-derived committed cardiac progenitors remuscularize damaged ischemic hearts and improve their function in pigs |
| title_short | Pluripotent stem cell-derived committed cardiac progenitors remuscularize damaged ischemic hearts and improve their function in pigs |
| title_sort | pluripotent stem cell derived committed cardiac progenitors remuscularize damaged ischemic hearts and improve their function in pigs |
| topic | Science::Medicine Cardiac Progenitors Heart Muscles |
| url | https://hdl.handle.net/10356/169965 |
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