Placental Mitochondria Therapy for Cerebral Ischemia-Reperfusion Injury in Mice

被引:70
|
作者
Nakamura, Yoshihiko
Lo, Eng H.
Hayakawa, Kazuhide
机构
[1] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA USA
[2] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA USA
[3] Harvard Med Sch, Charlestown, MA USA
关键词
membrane potentials; mitochondrial proteins; placenta; proof of concept study; stroke;
D O I
10.1161/STROKEAHA.120.030152
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background and Purpose: There is an urgent need to develop adjunct therapies that can be added onto reperfusion for acute ischemic stroke. Recently, mitochondrial transplantation has emerged as a promising therapeutic approach for boosting brain tissue protection. In this proof-of-concept study, we investigate the feasibility of using placenta as a source for mitochondrial transplantation in a mouse model of transient focal cerebral ischemia-reperfusion. Methods: Mitochondria-enriched fractions were isolated from cryopreserved mouse placenta. Mitochondrial purity and JC1 membrane potentials were assessed by flow cytometry. Adenosine triphosphate and mitochondrial proteins were measured by luminescence intensity and western blot, respectively. Therapeutic efficacy of mitochondrial fractions was assessed in a mouse model of transient focal cerebral ischemia-reperfusion. Results: Flow cytometry analysis demonstrated that about 87% of placental mitochondria were viable and maintained JC1 membrane potentials after isolation. Placental mitochondrial fractions contained adenosine triphosphate equivalent to mitochondrial fractions isolated from skeletal muscle and brown fat tissue. Normalized mitochondrial antioxidant enzymes (glutathione reductase, MnSOD [manganese superoxide dismutase]) and HSP70 (heat shock protein 70) were highly preserved in placental mitochondrial fractions. Treatment with placental mitochondrial fractions immediately after reperfusion significantly decreased infarction after focal cerebral ischemia in mice. Conclusions: Cryopreserved placenta can be a feasible source for viable mitochondrial isolation. Transplantation with placental mitochondria may amplify beneficial effects of reperfusion in stroke.
引用
收藏
页码:3142 / 3146
页数:5
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