Mesenchymal Stem/Stromal Cell-Mediated Mitochondrial Transfer and the Therapeutic Potential in Treatment of Neurological Diseases

Han, Deqiang; Zheng, Xin; Wang, Xueyao; Jin, Taiyi; Cui, Li; Chen, Zhiguo

doi:10.1155/2020/8838046

Cited by 32 publications

(39 citation statements)

References 134 publications

(162 reference statements)

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“…Simple co-incubation with mitochondria could be a more appropriate strategy for cell-based experiments, considering the distribution of injected mitochondria in the rat Achilles tendons. The co-incubation of mitochondria with tendon cells is also an intracellular mitochondrial delivery method [ 58 ]. Centrifugation, as an alternative to co-incubation, has a high transfer efficiency and reproducibility [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Transplantation Modulates Inflammation and Apoptosis, Alleviating Tendinopathy Both In Vivo and In Vitro

et al. 2021

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Tendinopathy is a common musculoskeletal condition causing pain and dysfunction. Conventional treatment and surgical procedures for tendinopathy are insufficient; accordingly, recent research has focused on tendon-healing regenerative approaches. Tendon injuries usually occur in the hypoxic critical zone, characterized by increased oxidative stress and mitochondrial dysfunction; thus, exogenous intact mitochondria may be therapeutic. We aimed to assess whether mitochondrial transplantation could induce anti-inflammatory activity and modulate the metabolic state of a tendinopathy model. Exogenous mitochondria were successfully delivered into damaged tenocytes by centrifugation. Levels of Tenomodulin and Collagen I in damaged tenocytes were restored with reductions in nuclear factor-κB and matrix metalloproteinase 1. The dysregulation of oxidative stress and mitochondrial membrane potential was attenuated by mitochondrial transplantation. Activated mitochondrial fission markers, such as fission 1 and dynamin-related protein 1, were dose-dependently downregulated. Apoptosis signaling pathway proteins were restored to the pre-damage levels. Similar changes were observed in a collagenase injection-induced rat model of tendinopathy. Exogenous mitochondria incorporated into the Achilles tendon reduced inflammatory and fission marker levels. Notably, collagen production was restored. Our results demonstrate the therapeutic effects of direct mitochondrial transplantation in tendinopathy. These effects may be explained by alterations in anti-inflammatory and apoptotic processes via changes in mitochondrial dynamics.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial Transplantation Modulates Inflammation and Apoptosis, Alleviating Tendinopathy Both In Vivo and In Vitro

et al. 2021

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“…This may describe a general mechanism of MSC action, since stem cell-derived donor mitochondria increased oxidative phosphorylation and ATP generation, and reduced ROS production in host cells like, e.g., myeloma cells [ 101 ], macrophages [ 102 ], cardiomyocytes [ 103 ], and airway epithelial cells [ 104 ]. Thus, the concept of MSC-derived mitochondrial transfer to improve recipient cell oxidative metabolism is now well established [ 105 ]. However, in our model of NASH, mechanistic questions remain open: How are diseased mitochondria cleared from the hepatocytes (e.g., by mitophagy)?…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Transfer by Human Mesenchymal Stromal Cells Ameliorates Hepatocyte Lipid Load in a Mouse Model of NASH

et al. 2020

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Mesenchymal stromal cell (MSC) transplantation ameliorated hepatic lipid load; tissue inflammation; and fibrosis in rodent animal models of non-alcoholic steatohepatitis (NASH) by as yet largely unknown mechanism(s). In a mouse model of NASH; we transplanted bone marrow-derived MSCs into the livers; which were analyzed one week thereafter. Combined metabolomic and proteomic data were applied to weighted gene correlation network analysis (WGCNA) and subsequent identification of key drivers. Livers were analyzed histologically and biochemically. The mechanisms of MSC action on hepatocyte lipid accumulation were studied in co-cultures of hepatocytes and MSCs by quantitative image analysis and immunocytochemistry. WGCNA and key driver analysis revealed that NASH caused the impairment of central carbon; amino acid; and lipid metabolism associated with mitochondrial and peroxisomal dysfunction; which was reversed by MSC treatment. MSC improved hepatic lipid metabolism and tissue homeostasis. In co-cultures of hepatocytes and MSCs; the decrease of lipid load was associated with the transfer of mitochondria from the MSCs to the hepatocytes via tunneling nanotubes (TNTs). Hence; MSCs may ameliorate lipid load and tissue perturbance by the donation of mitochondria to the hepatocytes. Thereby; they may provide oxidative capacity for lipid breakdown and thus promote recovery from NASH-induced metabolic impairment and tissue injury.

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“…MSCs can transfer mitochondria to injured cells with mitochondrial dysfunction through a variety of ways to restore cell aerobic respiration and mitochondria function, leading to rescue of cell injury ( Spees et al, 2006 ; Islam et al, 2012 ; Han et al, 2016 ). Mitochondrial dysfunction has been considered a sign of ischemia/reperfusion injury in the complex cell process, so mitochondrial transfer may be one of the mechanisms by which MSC treatment is of benefit for stroke ( Han et al, 2020 ). Co-cultured BM-MSCs can transfer intact mitochondria through transient tunneling nanotubes (TNT) to damaged cells, restoring their mitochondrial function ( Han et al, 2016 ).…”

Section: Potential Mechanisms Of Msc Therapy For Strokementioning

confidence: 99%

Mesenchymal Stem Cell-Based Therapy for Stroke: Current Understanding and Challenges

Liu

Shi

et al. 2021

Front. Cell. Neurosci.

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Stroke, the most prevalent cerebrovascular disease, causes serious loss of neurological function and is the leading cause of morbidity and mortality worldwide. Despite advances in pharmacological and surgical therapy, treatment for functional rehabilitation following stroke is limited with a consequent serious impact on quality of life. Over the past decades, mesenchymal stem cell (MSCs)-based therapy has emerged as a novel strategy for various diseases including stroke due to their unique properties that include easy isolation, multipotent differentiation potential and strong paracrine capacity. Although MSCs have shown promising results in the treatment of stroke, there remain many challenges to overcome prior to their therapeutic application. In this review, we focus on the following issues: the scientific data from preclinical studies and clinical trials of MSCs in the treatment of stroke; the potential mechanisms underlying MSC-based therapy for stroke; the challenges related to the timing and delivery of MSCs and MSC senescence.

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Mesenchymal Stem/Stromal Cell-Mediated Mitochondrial Transfer and the Therapeutic Potential in Treatment of Neurological Diseases

Cited by 32 publications

References 134 publications

Mitochondrial Transplantation Modulates Inflammation and Apoptosis, Alleviating Tendinopathy Both In Vivo and In Vitro

Mitochondrial Transplantation Modulates Inflammation and Apoptosis, Alleviating Tendinopathy Both In Vivo and In Vitro

Mitochondrial Transfer by Human Mesenchymal Stromal Cells Ameliorates Hepatocyte Lipid Load in a Mouse Model of NASH

Mesenchymal Stem Cell-Based Therapy for Stroke: Current Understanding and Challenges

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