Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies
Abstract Background Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation...
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2021-05-01
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Series: | Journal of Translational Medicine |
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Online Access: | https://doi.org/10.1186/s12967-021-02878-3 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kei Hayashida Ryosuke Takegawa Muhammad Shoaib Tomoaki Aoki Rishabh C. Choudhary Cyrus E. Kuschner Mitsuaki Nishikimi Santiago J. Miyara Daniel M. Rolston Sara Guevara Junhwan Kim Koichiro Shinozaki Ernesto P. Molmenti Lance B. Becker |
spellingShingle |
Kei Hayashida Ryosuke Takegawa Muhammad Shoaib Tomoaki Aoki Rishabh C. Choudhary Cyrus E. Kuschner Mitsuaki Nishikimi Santiago J. Miyara Daniel M. Rolston Sara Guevara Junhwan Kim Koichiro Shinozaki Ernesto P. Molmenti Lance B. Becker Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies Journal of Translational Medicine Systematic review Mitochondria Transplantation Ischemia reperfusion injury Translation science |
author_facet |
Kei Hayashida Ryosuke Takegawa Muhammad Shoaib Tomoaki Aoki Rishabh C. Choudhary Cyrus E. Kuschner Mitsuaki Nishikimi Santiago J. Miyara Daniel M. Rolston Sara Guevara Junhwan Kim Koichiro Shinozaki Ernesto P. Molmenti Lance B. Becker |
author_sort |
Kei Hayashida |
title |
Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies |
title_short |
Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies |
title_full |
Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies |
title_fullStr |
Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies |
title_full_unstemmed |
Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies |
title_sort |
mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies |
publisher |
BMC |
series |
Journal of Translational Medicine |
issn |
1479-5876 |
publishDate |
2021-05-01 |
description |
Abstract Background Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation. Methods We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis. Results Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI–associated myocardial dysfunction after cardiac surgery. Conclusion The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation. Systematic review registration The study was registered at UMIN under the registration number UMIN000043347. |
topic |
Systematic review Mitochondria Transplantation Ischemia reperfusion injury Translation science |
url |
https://doi.org/10.1186/s12967-021-02878-3 |
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doaj-1b29c76f8b1d46f6bb0e18fc3633b40e2021-05-23T11:11:09ZengBMCJournal of Translational Medicine1479-58762021-05-0119111510.1186/s12967-021-02878-3Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studiesKei Hayashida0Ryosuke Takegawa1Muhammad Shoaib2Tomoaki Aoki3Rishabh C. Choudhary4Cyrus E. Kuschner5Mitsuaki Nishikimi6Santiago J. Miyara7Daniel M. Rolston8Sara Guevara9Junhwan Kim10Koichiro Shinozaki11Ernesto P. Molmenti12Lance B. Becker13The Feinstein Institutes for Medical Research, Northwell Health SystemThe Feinstein Institutes for Medical Research, Northwell Health SystemThe Feinstein Institutes for Medical Research, Northwell Health SystemThe Feinstein Institutes for Medical Research, Northwell Health SystemThe Feinstein Institutes for Medical Research, Northwell Health SystemThe Feinstein Institutes for Medical Research, Northwell Health SystemThe Feinstein Institutes for Medical Research, Northwell Health SystemThe Feinstein Institutes for Medical Research, Northwell Health SystemDepartment of Emergency Medicine, North Shore University Hospital, Northwell Health SystemDepartment of Surgery, Northwell HealthThe Feinstein Institutes for Medical Research, Northwell Health SystemThe Feinstein Institutes for Medical Research, Northwell Health SystemZucker School of Medicine At Hofstra/NorthwellThe Feinstein Institutes for Medical Research, Northwell Health SystemAbstract Background Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation. Methods We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis. Results Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI–associated myocardial dysfunction after cardiac surgery. Conclusion The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation. Systematic review registration The study was registered at UMIN under the registration number UMIN000043347.https://doi.org/10.1186/s12967-021-02878-3Systematic reviewMitochondriaTransplantationIschemia reperfusion injuryTranslation science |