Case report: Transplantation of human induced pluripotent stem cell-derived cardiomyocyte patches for ischemic cardiomyopathy
Despite major therapeutic advances, heart failure, as a non-communicable disease, remains a life-threatening disorder, with 26 million patients worldwide, causing more deaths than cancer. Therefore, novel strategies for the treatment of heart failure continue to be an important clinical need. Based...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-08-01
|
| Series: | Frontiers in Cardiovascular Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.950829/full |
| _version_ | 1818483692322947072 |
|---|---|
| author | Shigeru Miyagawa Satoshi Kainuma Takuji Kawamura Kota Suzuki Yoshito Ito Hiroko Iseoka Emiko Ito Maki Takeda Masao Sasai Noriko Mochizuki-Oda Tomomi Shimamoto Yukako Nitta Hiromi Dohi Tadashi Watabe Yasushi Sakata Koichi Toda Yoshiki Sawa |
| author_facet | Shigeru Miyagawa Satoshi Kainuma Takuji Kawamura Kota Suzuki Yoshito Ito Hiroko Iseoka Emiko Ito Maki Takeda Masao Sasai Noriko Mochizuki-Oda Tomomi Shimamoto Yukako Nitta Hiromi Dohi Tadashi Watabe Yasushi Sakata Koichi Toda Yoshiki Sawa |
| author_sort | Shigeru Miyagawa |
| collection | DOAJ |
| description | Despite major therapeutic advances, heart failure, as a non-communicable disease, remains a life-threatening disorder, with 26 million patients worldwide, causing more deaths than cancer. Therefore, novel strategies for the treatment of heart failure continue to be an important clinical need. Based on preclinical studies, allogenic human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) patches have been proposed as a potential therapeutic candidate for heart failure. We report the implantation of allogeneic hiPSC-CM patches in a patient with ischemic cardiomyopathy (ClinicalTrials.gov, #jRCT2053190081). The patches were produced under clinical-grade conditions and displayed cardiogenic phenotypes and safety in vivo (severe immunodeficient mice) without any genetic mutations in cancer-related genes. The patches were then implanted via thoracotomy into the left ventricle epicardium of the patient under immunosuppressive agents. Positron emission tomography and computed tomography confirmed the potential efficacy and did not detect tumorigenesis in either the heart or other organs. The clinical symptoms improved 6 months after surgery, without any major adverse events, suggesting that the patches were well-tolerated. Furthermore, changes in the wall motion in the transplanted site were recovered, suggesting a favorable prognosis and the potential tolerance to exercise. This study is the first report of a successful transplant of hiPSC-CMs for severe ischemic cardiomyopathy. |
| first_indexed | 2024-12-10T15:45:17Z |
| format | Article |
| id | doaj.art-d2598ef6482f44ff824c95618be2a291 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-10T15:45:17Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-d2598ef6482f44ff824c95618be2a2912022-12-22T01:42:59ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-08-01910.3389/fcvm.2022.950829950829Case report: Transplantation of human induced pluripotent stem cell-derived cardiomyocyte patches for ischemic cardiomyopathyShigeru Miyagawa0Satoshi Kainuma1Takuji Kawamura2Kota Suzuki3Yoshito Ito4Hiroko Iseoka5Emiko Ito6Maki Takeda7Masao Sasai8Noriko Mochizuki-Oda9Tomomi Shimamoto10Yukako Nitta11Hiromi Dohi12Tadashi Watabe13Yasushi Sakata14Koichi Toda15Yoshiki Sawa16Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, JapanCenter for iPS Cell Research and Application, Kyoto University, Kyoto, JapanDepartment of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Suita, JapanDepartment of Cardiology, Osaka University Graduate School of Medicine, Suita, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, JapanDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, JapanDespite major therapeutic advances, heart failure, as a non-communicable disease, remains a life-threatening disorder, with 26 million patients worldwide, causing more deaths than cancer. Therefore, novel strategies for the treatment of heart failure continue to be an important clinical need. Based on preclinical studies, allogenic human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) patches have been proposed as a potential therapeutic candidate for heart failure. We report the implantation of allogeneic hiPSC-CM patches in a patient with ischemic cardiomyopathy (ClinicalTrials.gov, #jRCT2053190081). The patches were produced under clinical-grade conditions and displayed cardiogenic phenotypes and safety in vivo (severe immunodeficient mice) without any genetic mutations in cancer-related genes. The patches were then implanted via thoracotomy into the left ventricle epicardium of the patient under immunosuppressive agents. Positron emission tomography and computed tomography confirmed the potential efficacy and did not detect tumorigenesis in either the heart or other organs. The clinical symptoms improved 6 months after surgery, without any major adverse events, suggesting that the patches were well-tolerated. Furthermore, changes in the wall motion in the transplanted site were recovered, suggesting a favorable prognosis and the potential tolerance to exercise. This study is the first report of a successful transplant of hiPSC-CMs for severe ischemic cardiomyopathy.https://www.frontiersin.org/articles/10.3389/fcvm.2022.950829/fullhuman induced pluripotent stem cell-derived cardiomyocyteischemic cardiomyopathytransplantationregenerative therapyclinical trial |
| spellingShingle | Shigeru Miyagawa Satoshi Kainuma Takuji Kawamura Kota Suzuki Yoshito Ito Hiroko Iseoka Emiko Ito Maki Takeda Masao Sasai Noriko Mochizuki-Oda Tomomi Shimamoto Yukako Nitta Hiromi Dohi Tadashi Watabe Yasushi Sakata Koichi Toda Yoshiki Sawa Case report: Transplantation of human induced pluripotent stem cell-derived cardiomyocyte patches for ischemic cardiomyopathy Frontiers in Cardiovascular Medicine human induced pluripotent stem cell-derived cardiomyocyte ischemic cardiomyopathy transplantation regenerative therapy clinical trial |
| title | Case report: Transplantation of human induced pluripotent stem cell-derived cardiomyocyte patches for ischemic cardiomyopathy |
| title_full | Case report: Transplantation of human induced pluripotent stem cell-derived cardiomyocyte patches for ischemic cardiomyopathy |
| title_fullStr | Case report: Transplantation of human induced pluripotent stem cell-derived cardiomyocyte patches for ischemic cardiomyopathy |
| title_full_unstemmed | Case report: Transplantation of human induced pluripotent stem cell-derived cardiomyocyte patches for ischemic cardiomyopathy |
| title_short | Case report: Transplantation of human induced pluripotent stem cell-derived cardiomyocyte patches for ischemic cardiomyopathy |
| title_sort | case report transplantation of human induced pluripotent stem cell derived cardiomyocyte patches for ischemic cardiomyopathy |
| topic | human induced pluripotent stem cell-derived cardiomyocyte ischemic cardiomyopathy transplantation regenerative therapy clinical trial |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.950829/full |
| work_keys_str_mv | AT shigerumiyagawa casereporttransplantationofhumaninducedpluripotentstemcellderivedcardiomyocytepatchesforischemiccardiomyopathy AT satoshikainuma casereporttransplantationofhumaninducedpluripotentstemcellderivedcardiomyocytepatchesforischemiccardiomyopathy AT takujikawamura casereporttransplantationofhumaninducedpluripotentstemcellderivedcardiomyocytepatchesforischemiccardiomyopathy AT kotasuzuki casereporttransplantationofhumaninducedpluripotentstemcellderivedcardiomyocytepatchesforischemiccardiomyopathy AT yoshitoito casereporttransplantationofhumaninducedpluripotentstemcellderivedcardiomyocytepatchesforischemiccardiomyopathy AT hirokoiseoka casereporttransplantationofhumaninducedpluripotentstemcellderivedcardiomyocytepatchesforischemiccardiomyopathy AT emikoito casereporttransplantationofhumaninducedpluripotentstemcellderivedcardiomyocytepatchesforischemiccardiomyopathy AT makitakeda casereporttransplantationofhumaninducedpluripotentstemcellderivedcardiomyocytepatchesforischemiccardiomyopathy AT masaosasai casereporttransplantationofhumaninducedpluripotentstemcellderivedcardiomyocytepatchesforischemiccardiomyopathy AT norikomochizukioda casereporttransplantationofhumaninducedpluripotentstemcellderivedcardiomyocytepatchesforischemiccardiomyopathy AT tomomishimamoto casereporttransplantationofhumaninducedpluripotentstemcellderivedcardiomyocytepatchesforischemiccardiomyopathy AT yukakonitta casereporttransplantationofhumaninducedpluripotentstemcellderivedcardiomyocytepatchesforischemiccardiomyopathy AT hiromidohi casereporttransplantationofhumaninducedpluripotentstemcellderivedcardiomyocytepatchesforischemiccardiomyopathy AT tadashiwatabe casereporttransplantationofhumaninducedpluripotentstemcellderivedcardiomyocytepatchesforischemiccardiomyopathy AT yasushisakata casereporttransplantationofhumaninducedpluripotentstemcellderivedcardiomyocytepatchesforischemiccardiomyopathy AT koichitoda casereporttransplantationofhumaninducedpluripotentstemcellderivedcardiomyocytepatchesforischemiccardiomyopathy AT yoshikisawa casereporttransplantationofhumaninducedpluripotentstemcellderivedcardiomyocytepatchesforischemiccardiomyopathy |