Stem cell-derived mitochondria transplantation: a novel strategy and the challenges for the treatment of tissue injury

Wang, Jingyu; Li, Heyangzi; Yao, Ying; Zhao, Tengfei; Chen, Yingying; Shen, Yue‐Liang; Wang, Linlin; Zhu, Yongjian

doi:10.1186/s13287-018-0832-2

Cited by 73 publications

(64 citation statements)

References 88 publications

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“…40 Clinical transplantation of mitochondria between cells is an active area of research but the specific mechanisms and critical factors involved in natural mitochondria transfer between the donor cells and recipient cells remain to be fully characterized. 41 We speculate that mitochondrial clearance and degradation occurs principally by phagocytosis. This study is the first showing free structurally intact mitochondria in plasma, but it is not yet known how they are degraded there, in contrast to intracellular mitophagy, which is well described.…”

Section: Discussionmentioning

confidence: 93%

Blood contains circulating cell‐free respiratory competent mitochondria

et al. 2020

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Mitochondria are considered as the power‐generating units of the cell due to their key role in energy metabolism and cell signaling. However, mitochondrial components could be found in the extracellular space, as fragments or encapsulated in vesicles. In addition, this intact organelle has been recently reported to be released by platelets exclusively in specific conditions. Here, we demonstrate for the first time, that blood preparation with resting platelets, contains whole functional mitochondria in normal physiological state. Likewise, we show, that normal and tumor cultured cells are able to secrete their mitochondria. Using serial centrifugation or filtration followed by polymerase chain reaction‐based methods, and Whole Genome Sequencing, we detect extracellular full‐length mitochondrial DNA in particles over 0.22 µm holding specific mitochondrial membrane proteins. We identify these particles as intact cell‐free mitochondria using fluorescence‐activated cell sorting analysis, fluorescence microscopy, and transmission electron microscopy. Oxygen consumption analysis revealed that these mitochondria are respiratory competent. In view of previously described mitochondrial potential in intercellular transfer, this discovery could greatly widen the scope of cell‐cell communication biology. Further steps should be developed to investigate the potential role of mitochondria as a signaling organelle outside the cell and to determine whether these circulating units could be relevant for early detection and prognosis of various diseases.

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Section: Discussionmentioning

confidence: 93%

Blood contains circulating cell‐free respiratory competent mitochondria

et al. 2020

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“…To assess the cause-effect relationship for mitochondrial dysfunction in SCZ, Robicek et al [ 84 ] most recently investigated mitochondria transfer to SCZ-iPSC derived neurons [ 78 ]. Several studies have shown that mitochondria can transfer between cells via various contact modes, comprising cell fusion, junction, and tunneling nanotube formation [ 103 ]. In support of these findings, Robicek et al observed that in vitro isolated active normal mitochondria (IAN-MIT) can enter various cell types without any manipulation and stay active.…”

Section: Introductionmentioning

confidence: 99%

Tracing Early Neurodevelopment in Schizophrenia with Induced Pluripotent Stem Cells

Ahmad

Sportelli

Ziller

et al. 2018

Cells

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Schizophrenia (SCZ) is a devastating mental disorder that is characterized by distortions in thinking, perception, emotion, language, sense of self, and behavior. Epidemiological evidence suggests that subtle perturbations in early neurodevelopment increase later susceptibility for disease, which typically manifests in adolescence to early adulthood. Early perturbations are thought to be significantly mediated through incompletely understood genetic risk factors. The advent of induced pluripotent stem cell (iPSC) technology allows for the in vitro analysis of disease-relevant neuronal cell types from the early stages of human brain development. Since iPSCs capture each donor’s genotype, comparison between neuronal cells derived from healthy and diseased individuals can provide important insights into the molecular and cellular basis of SCZ. In this review, we discuss results from an increasing number of iPSC-based SCZ/control studies that highlight alterations in neuronal differentiation, maturation, and neurotransmission in addition to perturbed mitochondrial function and micro-RNA expression. In light of this remarkable progress, we consider also ongoing challenges from the field of iPSC-based disease modeling that call for further improvements on the generation and design of patient-specific iPSC studies to ultimately progress from basic studies on SCZ to tailored treatments.

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“…Mitochondria-targeting treatment, considered to be an appealing strategy for the control and management of mitochondrial injury [41], has become the focus of many important research studies [42]. Previously-published data have suggested that the injection of isolated viable respiration-competent myocardial mitochondria into ischemic regions prior to reperfusion may reverse post-ischemic functional deterioration and apoptosis, thereby limiting the infarct area [43].…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture pretreatment alleviates myocardial injury through regulating mitochondrial function

Wang

Liang

et al. 2020

Preprint

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Abstract Electroacupuncture is well known for its advantageous neuroanalgesic and therapeutic effects on myocardial ischemia-reperfusion injury. The purpose of the present research was to verify whether electroacupuncture can alleviate bupivacaine-induced myocardial injury. Methods Specific-pathogen-free Wistar rats were used to establish the bupivacaine-induced myocardial injury model. Western blot, PCR, transmission electron microscope and enzyme-linked immunosorbent (ELISA) methods were used to evaluate bupivacaine-induced structure injury and dysfunction of the mitochondria as well as the alleviating effects of lipid emulsion, acupoint injection, and electroacupuncture pre-treatment of the oxidase stress response. Results Bupivacaine caused structural damage, degradation, and swelling of mitochondria. Furthermore, it reduced adenosine triphosphate (ATP) synthesis and impaired energy metabolism in the mitochondria. Structural and functional impairment of the mitochondria was alleviated via lipid emulsion injection, acupoint injection, and electroacupuncture pre-treatment. Electroacupuncture pre-treatment of PC6 yielded a greater alleviating effect than others approaches. Following electroacupuncture pre-treatment of PC6 point, the number of mitochondria increased; apoptosis was reduced, enzymatic activity of cytochrome C oxidase (COX) and superoxide dismutase and expression of uncoupling protein 2, voltage-dependent anion channel 1, and Bcl 2 were upregulated and SLC25A6, MDA levels were downregulated. Additionally, our findings indicated that electroacupuncture pre-treatment of PC6 point exerted an effect on the mitochondria via the mitochondrial-transcription-factor-A / nuclear-respiratory-factor-1 / proliferator-activated-receptor-gamma-coactivator -1 pathway. Conclusion The present study revealed that electroacupuncture pre-treatment of PC6 could effectively alleviate bupivacaine-induced myocardial mitochondrial damage, thereby providing a theoretical basis for clinical studies and applications of this treatment method.

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Stem cell-derived mitochondria transplantation: a novel strategy and the challenges for the treatment of tissue injury

Cited by 73 publications

References 88 publications

Blood contains circulating cell‐free respiratory competent mitochondria

Blood contains circulating cell‐free respiratory competent mitochondria

Tracing Early Neurodevelopment in Schizophrenia with Induced Pluripotent Stem Cells

Electroacupuncture pretreatment alleviates myocardial injury through regulating mitochondrial function

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