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2016 ; 5
(1
): 16
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Mitochondrial transplantation for therapeutic use
#MMPMID27130633
McCully JD
; Levitsky S
; Del Nido PJ
; Cowan DB
Clin Transl Med
2016[Mar]; 5
(1
): 16
PMID27130633
show ga
Mitochondria 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.
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