Muscle-derived autologous mitochondrial transplantation: A novel strategy for treating cerebral ischemic injury

Zhang, Zhanqin; Ma, Zhi; Yan, Chaoying; Pu, Kairui; Wu, Mingyan; Bai, Juan; Li, Yansong; Wang, Qiang

doi:10.1016/j.bbr.2018.09.005

Cited by 93 publications

(87 citation statements)

References 41 publications

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“…As a matter of fact, mitochondria transplantation has been successfully tested in several animal models for mitochondrial diseases. In particular, this therapeutic approach has been invariably shown to significantly reduce hypoxic/ischemic insult and restore tissue function following myocardial infarction [ 173 , 174 , 175 , 176 ], acute kidney injury [ 177 ], stroke [ 178 , 179 ], spinal cord injury [ 180 , 181 ], or optic nerve crush leading to glaucoma [ 182 ] by improving the bioenergetics and cell survival and by decreasing oxidative stress and mitochondrial DNA damages. Similarly, mitochondria transplantation has been reported to exert beneficial effects in animal models for either metabolic syndromes, including diabetic ischemic heart [ 183 ] and non-alcoholic fatty liver [ 184 ], or for neurological disorders, such as Parkinson’s disease [ 185 , 186 ] and schizophrenia [ 187 ].…”

Section: Current Therapeutic Approaches and Clinical Trials For Thmentioning

confidence: 99%

Multifaceted Roles of Mitochondrial Components and Metabolites in Metabolic Diseases and Cancer

Nakhle

Rodriguez

Vignais

2020

IJMS

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Mitochondria are essential cellular components that ensure physiological metabolic functions. They provide energy in the form of adenosine triphosphate (ATP) through the electron transport chain (ETC). They also constitute a metabolic hub in which metabolites are used and processed, notably through the tricarboxylic acid (TCA) cycle. These newly generated metabolites have the capacity to feed other cellular metabolic pathways; modify cellular functions; and, ultimately, generate specific phenotypes. Mitochondria also provide intracellular signaling cues through reactive oxygen species (ROS) production. As expected with such a central cellular role, mitochondrial dysfunctions have been linked to many different diseases. The origins of some of these diseases could be pinpointed to specific mutations in both mitochondrial- and nuclear-encoded genes. In addition to their impressive intracellular tasks, mitochondria also provide intercellular signaling as they can be exchanged between cells, with resulting effects ranging from repair of damaged cells to strengthened progression and chemo-resistance of cancer cells. Several therapeutic options can now be envisioned to rescue mitochondria-defective cells. They include gene therapy for both mitochondrial and nuclear defective genes. Transferring exogenous mitochondria to target cells is also a whole new area of investigation. Finally, supplementing targeted metabolites, possibly through microbiota transplantation, appears as another therapeutic approach full of promises.

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Section: Current Therapeutic Approaches and Clinical Trials For Thmentioning

confidence: 99%

Multifaceted Roles of Mitochondrial Components and Metabolites in Metabolic Diseases and Cancer

Nakhle

Rodriguez

Vignais

2020

IJMS

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“…Therefore, the transplantation of exogenous mitochondria may be an excellent option to treat ischemic stroke-induced brain injury. Subsequently, the results from different groups [30,31] suggested that the replenishment of exogenous mitochondria can signi cantly alleviate tMCAO-induced brain injury, as indicated by improved neurological outcomes and brain infarct volume due to the reduction of oxidative stress (OS), reactive astrogliosis, apoptosis and the promotion of neurogenesis. In our present study, we obtained comparable results in that the delivery of Neuro-2a cellderived mitochondria could signi cantly improve tMCAO-induced neurological de cits and brain infarction size.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the transplantation of exogenous mitochondria has been intensively investigated as a therapeutic strategy and has demonstrated bene cial effects for various kinds types human disorders, including I/R injury (acute lung injury (ALI) [12], liver injury [13,14], heart injury [15][16][17][18][19] and limb injury [20]), acetaminophen-induced liver disorder [21], non-alcoholic fatty liver disease [22], breast cancer [23][24][25], and lung diseases (pulmonary artery hypertension [26], hyperresponsiveness of the airway [27]). Furthermore, the transplantation of exogenous mitochondria has been reported to be capable of improving multiple central nervous system (CNS) disorders [28,29] such as stroke [30,31], spinal cord injury (SCI) [32,33], schizophrenia [34], depression-like behaviors [35] and neurodegenerative diseases such as Parkinson's disease (PD) [36,37].…”

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confidence: 99%

Mitochondrial Transplantation Improves Stroke-Induced Brain Injury: Possible Involvement of Selective Component Recombination

Xie¹,

Zeng²,

Xu³

et al. 2020

Preprint

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Background: Ischemic stroke results in high morbidity and mortality, and mitochondrial dysfunctions play a crucial role in the associated pathological process. Although exogenous mitochondria were used to treat ischemic stroke-induced brain injury, its effects and related mechanisms remain poorly understood, as is the fate of exogenous mitochondria during/after internalization by targeted cells. Methods: The mitochondrial morphology, membrane potential, DNA copy number, mitochondrial stress, metabolic characteristics and tumorigenicity of mNSCs and Neuro-2a cells were evaluated. Hypoxia/reoxygenation-induced cell injury was performed, and after mitochondrial supplementation, the viability, ROS levels, apoptosis and transcriptomic changes were assessed by CCK-8, DCHF-DA probes, flow cytometry, WB and next-generation sequencing analyses. The fate of exogenous mitochondria was further explored using fluorescent dyes and fusion protein analyses during/after internalization by targeted cells. Rat tMCAO models were generated using a suture-occluded method, and at 24 h after mitochondrial transplantation, behavioral changes and brain infarction areas were estimated by multiple score scales and TTC staining, respectively. Results: In this research, we found that mitochondria of Neuro-2a cells had some notable differences compared to that of mNSCs on mitochondrial membrane potential, DNA copy number, stress response and metabolic characteristics, but their shapes were similar and were both no tumorigenicity. Exogenous mitochondrial treatment could increase the cellular viability in an oxygen-dependent pattern, decrease the cellular ROS generation and apoptosis, and alter the transcriptomic characteristics after subjected to hypoxia/reoxygenation in vitro. Selective component recombination might occur during/after internalization of exogenous mitochondria by host cells and was observed with mitochondrial fluorescent dyes and engineered fusion protein. Moreover, mitochondrial transplantation could significantly improve tMCAO-induced rat neurobehavioral deficiency and brain infarction. Conclusions: The results of our present study offer a promising therapeutic strategy for ischemia/reperfusion-induced brain injury and provide preliminary insights regarding the effects and fate of exogenous mitochondria during/after being internalized into host cells.

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“…This represents a protective mechanism that promotes oxidative resistance and a repair function. Although very important questions need to be answered regarding AMT/T, hypothesizing that isolated mitochondria could be internalized by melanocytes to help cells produce energy more efficiently, less ROS ( Zhang et al, 2019 ), and ultimately fewer mutations are plausible.…”

Section: Amt/t For the Antiaging Use Of Mitochondriamentioning

confidence: 99%

Bases for Treating Skin Aging With Artificial Mitochondrial Transfer/Transplant (AMT/T)

Balcázar

Cañizares

Borja

et al. 2020

Front. Bioeng. Biotechnol.

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The perception of mitochondria as only the powerhouse of the cell has dramatically changed in the last decade. It is now accepted that in addition to being essential intracellularly, mitochondria can promote cellular repair when transferred from healthy to damaged cells. The artificial mitochondria transfer/transplant (AMT/T) group of techniques emulate this naturally occurring process and have been used to develop therapies to treat a range of diseases including cardiac and neurodegenerative. Mitochondria accumulate damage with time, resulting in cellular senescence. Skin cells and its mitochondria are profoundly affected by ultraviolet radiation and other factors that induce premature and accelerated aging. In this article, we propose the basis to use AMT/T to treat skin aging by transferring healthy mitochondria to senescent cells, possibly revitalizing them. We provide insightful information about how skin structure, components, and cells could age rapidly depending on the amount of damage received. Arguments are shown in favor of the use of AMT/T to treat aging skin and its cells, among them the possibility to stop free radical production, add new genetic material, and provide an energetic boost to help cells prolong their viability over time. This article intends to present one of the many aspects in which mitochondria could be used as a universal treatment for cell and tissue damage and aging.

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Muscle-derived autologous mitochondrial transplantation: A novel strategy for treating cerebral ischemic injury

Cited by 93 publications

References 41 publications

Multifaceted Roles of Mitochondrial Components and Metabolites in Metabolic Diseases and Cancer

Multifaceted Roles of Mitochondrial Components and Metabolites in Metabolic Diseases and Cancer

Mitochondrial Transplantation Improves Stroke-Induced Brain Injury: Possible Involvement of Selective Component Recombination

Bases for Treating Skin Aging With Artificial Mitochondrial Transfer/Transplant (AMT/T)

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