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dc.contributor.authorMcCully, James Donald
dc.contributor.authorLevitsky, Sidney
dc.contributor.authorDel Nido, Pedro J.
dc.contributor.authorCowan, Douglas Burr
dc.date.accessioned2016-06-21T15:21:36Z
dc.date.issued2016
dc.identifier.citationMcCully, James D., Sidney Levitsky, Pedro J. del Nido, and Douglas B. Cowan. 2016. “Mitochondrial Transplantation for Therapeutic Use.” Clin Trans Med 5 (1) (April 29). doi:10.1186/s40169-016-0095-4.en_US
dc.identifier.issn2001-1326en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:27364124
dc.description.abstractMitochondria play a key role in the homeostasis of the vast majority of the body’s cells. In the myocardium where mitochondria constitute 30 % of the total myocardial cell volume, temporary attenuation or obstruction of blood flow and as a result oxygen delivery to myocardial cells (ischemia) severely alters mitochondrial structure and function. These alterations in mitochondrial structure and function occur during ischemia and continue after blood flow and oxygen delivery to the myocardium is restored, and significantly decrease myocardial contractile function and myocardial cell survival. We hypothesized that the augmentation or replacement of mitochondria damaged by ischemia would provide a mechanism to enhance cellular function and cellular rescue following the restoration of blood flow. To test this hypothesis we have used a model of myocardial ischemia and reperfusion. Our studies demonstrate that the transplantation of autologous mitochondria, isolated from the patient’s own body, and then directly injected into the myocardial during early reperfusion augment the function of native mitochondria damaged during ischemia and enhances myocardial post-ischemic functional recovery and cellular viability. The transplanted mitochondria act both extracellularly and intracellularly. Extracellularly, the transplanted mitochondria enhance high energy synthesis and cellular adenosine triphosphate stores and alter the myocardial proteome. Once internalized the transplanted mitochondria rescue cellular function and replace damaged mitochondrial DNA. There is no immune or auto-immune reaction and there is no pro-arrhythmia as a result of the transplanted mitochondria. Our studies and those of others demonstrate that mitochondrial transplantation can be effective in a number of cell types and diseases. These include cardiac and skeletal muscle, pulmonary and hepatic tissue and cells and in neuronal tissue. In this review we discuss the mechanisms leading to mitochondrial dysfunction and the effects on cellular function. We provide a methodology for the isolation of mitochondria to allow for clinical relevance and we discuss the methods we and others have used for the uptake and internalization of mitochondria. We foresee that mitochondrial transplantation will be a valued treatment in the armamentarium of all clinicians and surgeons for the treatment of varied ischemic disorders, mitochondrial diseases and related disorders.en_US
dc.language.isoen_USen_US
dc.publisherSpringer Science + Business Mediaen_US
dc.relation.isversionofdoi:10.1186/s40169-016-0095-4en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851669/en_US
dash.licenseLAA
dc.subjectIschemia/reperfusion injuryen_US
dc.subjectMitochondriaen_US
dc.subjectMyocardiumen_US
dc.subjectSurgeryen_US
dc.titleMitochondrial transplantation for therapeutic useen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalClinical and Translational Medicineen_US
dash.depositing.authorMcCully, James Donald
dc.date.available2016-06-21T15:21:36Z
dc.identifier.doi10.1186/s40169-016-0095-4*
dash.authorsorderedfalse
dash.contributor.affiliatedMcCully, James
dash.contributor.affiliatedCowan, Douglas
dash.contributor.affiliatedLevitsky, Sidney
dash.contributor.affiliatedDel Nido, Pedro


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