Mitochondrial transplantation by intra-arterial injection for acute kidney injury

Abstract

Acute kidney injury (AKI) is a common clinical disorder and one of the major causes of morbidity and mortality in the postoperative period. In this study, the safety and efficacy of autologous mitochondrial transplantation by intra-arterial injection for renal protection in a swine model of bilateral renal ischemia-reperfusion injury (IRI) was investigated. Female Yorkshire pigs underwent percutaneous bilateral temporary occlusion of the renal arteries with balloon-catheters. Following 60 minutes ischemia, the balloon catheters were deflated and the animals received either autologous mitochondria suspended in vehicle or vehicle alone, delivered as a single bolus to the renal arteries. The injected mitochondria were rapidly taken up by the kidney and were distributed throughout the tubular epithelium of cortex and medulla. There were no safety related issues detected with mitochondrial transplantation. Following 24 hours of reperfusion, estimated glomerular filtration rate and urine output were significantly increased while serum creatinine and blood urea nitrogen were significantly decreased in swine receiving mitochondria as compared to those receiving vehicle. Gross anatomy, histopathological analysis, acute tubular necrosis scoring and transmission electron microscopy showed that the renal cortex of vehicle group had extensive coagulative necrosis of primarily proximal tubules, while the mitochondrial transplanted kidney showed only patchy mild acute tubular injury. Renal cortex IL-6 expression was significantly increased in Vehicle kidneys as compared to the kidneys receiving mitochondrial transplantation. These results demonstrate that mitochondrial transplantation by intra-arterial injection provides renal protection from IRI, significantly enhancing renal function and reducing renal damage.

Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies

“…There were two studies on experimental models of kidney focal ischemia in rats [ 43 ] and pigs [ 44 ], in which autologous mitochondria were injected intra-arterially.…”

“…Jabbari et al [ 43 ] demonstrated that mitochondrial autografts from healthy muscle cells to injured kidney cells through injection into the renal artery prevented renal tubular cell death, restored renal function, ameliorated kidney damage, improved the regenerative potential of renal tubules, and decreased IRI-induced apoptosis [ 43 ]. Doulamis et al [ 44 ] investigated the safety and efficacy of autologous mitochondrial transplantation by intra-arterial injection for renal protection in a swine model of bilateral renal IRI. They found that the injected mitochondria were rapidly taken up by the kidneys.…”

“Empowering” Cardiac Cells via Stem Cell Derived Mitochondrial Transplantation- Does Age Matter?

“…In contrast to aging alterations the effect of diseases like diabetes on mitochondria is less clear [ 103 ]: Minet et al found in vitro impaired mitochondrial functions in type 2 diabetes-derived myotubes due to impaired ATP synthesis [ 104 ]. In diabetic rats, mitochondrial ATP content was lower compared to healthy individuals, whereas no obvious functional cardiac differences were seen [ 105 ]. In pathological diabetic conditions changes in morphology, superoxide production, cardiolipin content and dysfunctional mitochondrial protein import were seen in IMF of type 1 diabetic mice [ 106 , 107 , 108 ], whereas in type 2 diabetes the SSM seem to be more affected [ 109 ].…”

“…Mitochondrial transplantations have been so far successfully used in neurological fields [ 118 , 119 ], liver infarcts, kidney injuries [ 105 ], acute lung injury [ 120 ], acute limb injury [ 121 ] and in various cardiovascular settings. Especially in the field of cardiovascular research, interesting studies have been published during the course of the last years.…”

“…Especially in the field of cardiovascular research, interesting studies have been published during the course of the last years. Based on promising effects of experiments in vitro latest in vivo studies particularly by the group of McCully have been published [ 4 , 64 , 105 , 114 , 115 , 116 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 ]. Table 1 gives an overview of the literature using mitochondrial transplantation for the treatment of cardiovascular diseases.…”