Mesenchymal stem cells-derived mitochondria transplantation mitigates I/R-induced injury, abolishes I/R-induced apoptosis, and restores motor function in acute ischemia stroke rat model

Pourmohammadi-Bejarpasi, Zahra; Roushandeh, Amaneh Mohammadi; Saberi, Alia; Rostami, Mojdeh Kheirandish; Toosi, Seyyed Mohammadtaghi Razavi; Jahanian-Najafabadi, Ali; Tomita, Kazuo; Kuwahara, Yoshikazu; Sato, Tomoaki; Roudkenar, Mehryar Habibi

doi:10.1016/j.brainresbull.2020.09.018

Cited by 61 publications

(32 citation statements)

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“…Five experimental models targeting brain injury were generated in mice [ 25 ] and rats [ 30 – 33 ], including four focal brain ischemia models (middle cerebral artery occlusion [MCAO]) [ 25 , 31 – 33 ] and one traumatic brain injury (TBI) model [ 30 ]. The types of transplantation used were autologous [ 32 ], allograft [ 25 , 30 ], and xenograft [ 31 , 33 ]. The types of administration were direct or near-direct injection [ 30 – 33 ] and intravenous [ 25 ].…”

Section: Resultsmentioning

confidence: 99%

“…Excess reactive oxygen species and oxidative stress are major contributors to brain damage following acute ischemic stroke. Pourmohammadi-Bejarpasi et al [ 31 ] reported the intracerebroventricular transplantation of isolated mitochondria from human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in a rat model of MCAO. MCAO occlusion in rats for 70 min followed by reperfusion and mitochondrial transplantation demonstrated normal brain cytoarchitecture and neurons with a decreased number of pyknotic cells [ 31 ].…”

Section: Resultsmentioning

confidence: 99%

“…Pourmohammadi-Bejarpasi et al [ 31 ] reported the intracerebroventricular transplantation of isolated mitochondria from human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in a rat model of MCAO. MCAO occlusion in rats for 70 min followed by reperfusion and mitochondrial transplantation demonstrated normal brain cytoarchitecture and neurons with a decreased number of pyknotic cells [ 31 ]. Brain injury after acute stroke can result in astrocyte hypertrophy, and the subsequent release of glial fibrillary acidic protein (GFAP) can lead to scar formation, thus limiting neuronal recovery.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2021

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Background Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation. Methods We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis. Results Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI–associated myocardial dysfunction after cardiac surgery. Conclusion The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation. Systematic review registration The study was registered at UMIN under the registration number UMIN000043347.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

et al. 2021

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“…Additionally, the role of Miro1 in mitochondrial transfer has also been disclosed, where increasing Miro1 expression in MSCs improved the efficiency of mitochondrial transfer into the neurons and astrocytes (Babenko et al, 2018;Tseng et al, 2020). Generally, the replenishing of healthy mitochondria of the damaged neural cells is capable of enhancing oxidative phosphorylation, decreasing cellular oxidative stress level, and then alleviating the brain disaster cascade following cerebral ischemia (Pourmohammadi-Bejarpasi et al, 2020). Based on the foregoing discussion, MSCs exert antioxidant capacity in ischemic stroke mainly via reducing oxidative stress level and transferring healthy mitochondria.…”

Section: Msc-mediated Mitochondrial Transfermentioning

confidence: 99%

Oxidative Stress, Inflammation, and Autophagy: Potential Targets of Mesenchymal Stem Cells-Based Therapies in Ischemic Stroke

Liu

Huang

et al. 2021

Front. Neurosci.

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Ischemic stroke is a leading cause of death worldwide; currently available treatment approaches for ischemic stroke are to restore blood flow, which reduce disability but are time limited. The interruption of blood flow in ischemic stroke contributes to intricate pathophysiological processes. Oxidative stress and inflammatory activity are two early events in the cascade of cerebral ischemic injury. These two factors are reciprocal causation and directly trigger the development of autophagy. Appropriate autophagy activity contributes to brain recovery by reducing oxidative stress and inflammatory activity, while autophagy dysfunction aggravates cerebral injury. Abundant evidence demonstrates the beneficial impact of mesenchymal stem cells (MSCs) and secretome on cerebral ischemic injury. MSCs reduce oxidative stress through suppressing reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation and transferring healthy mitochondria to damaged cells. Meanwhile, MSCs exert anti-inflammation properties by the production of cytokines and extracellular vesicles, inhibiting proinflammatory cytokines and inflammatory cells activation, suppressing pyroptosis, and alleviating blood–brain barrier leakage. Additionally, MSCs regulation of autophagy imbalances gives rise to neuroprotection against cerebral ischemic injury. Altogether, MSCs have been a promising candidate for the treatment of ischemic stroke due to their pleiotropic effect.

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“…Mesenchymal stem cell transplantation has been shown to modulate immunological effects through the production of anti-inflammatory cytokines, including IL-10 and IL-13, and to stimulate neurosupportive effects by secreting factors including basic fibroblast growth factor and vascular endothelial growth factor [138][139][140][141][142]. In addition, mesenchymal stem cells may restore mitochondrial function in skeletal muscle via the mediation of mitochondrial transplantation [143]. However, stem cell transplantation has many restrictive hurdles to overcome (e.g., controversial safety and efficacy, ethics, pharmaceutical manufacturing process, and quality control); the secretome of stem cells that houses the important anti-inflammatory agents may provide a more promising option than the direct use of stem cells [137].…”

Section: Regenerative Therapeutic Approach: Mitochondrial Restoration and Anti-inflammationmentioning

confidence: 99%

Emerging Treatment Options for Sarcopenia in Chronic Liver Disease

Kim

2021

Life

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Sarcopenia is characterized by a skeletal muscle disorder with progressive and generalized loss of muscle mass and function, and it increases the risk of adverse outcomes with considerable prevalence in patients with chronic liver disease. Sarcopenia in chronic liver disease underlies complicated and multifactorial mechanisms for pathogenesis, including alterations in protein turnover, hyperammonemia, energy disposal, hormonal changes, and chronic inflammation. The key contribution to sarcopenia in patients with chronic liver diseases can be the hyperammonemia-induced upregulation of myostatin, which causes muscle atrophy via the expression of atrophy-related genes. Several clinical studies on emerging treatment options for sarcopenia have been reported, but only a few have focused on patients with chronic liver diseases, with mostly nutritional and behavioral interventions being carried out. The inhibition of the myostatin-activin receptor signaling pathway and hormonal therapy might be the most promising therapeutic options in combination with an ammonia-lowering approach in sarcopenic patients with chronic liver diseases. This review focuses on current and emerging treatment options for sarcopenia in chronic liver diseases with underlying mechanisms to counteract this condition.

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Mesenchymal stem cells-derived mitochondria transplantation mitigates I/R-induced injury, abolishes I/R-induced apoptosis, and restores motor function in acute ischemia stroke rat model

Cited by 61 publications

References 31 publications

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

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

Oxidative Stress, Inflammation, and Autophagy: Potential Targets of Mesenchymal Stem Cells-Based Therapies in Ischemic Stroke

Emerging Treatment Options for Sarcopenia in Chronic Liver Disease

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