Mesenchymal stem cells alleviate oxidative stress–induced mitochondrial dysfunction in the airways

Li, Xiang; Michaeloudes, Charalambos; Zhang, Yuelin; Wiegman, Coen; Adcock, Ian M.; Lian, Qizhou; Mak, Judith C.W.; Bhavsar, Pankaj; Chung, Kian Fan

doi:10.1016/j.jaci.2017.08.017

Cited by 115 publications

(93 citation statements)

References 40 publications

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“…Our advanced, deep bioinformatic analysis overcame some limitations in capture and coverage of WES, leading to a high diagnostic yield rate. Uncovering molecular defects can help us understand the complex pathogenesis of LS, paving the way for development of curative treatment options and potential therapeutic strategies, including stem cell‐derived mitochondrial donation or CRISPR/Cas9 genome editing . In genetically unsolved cases, RNA sequencing of muscle biopsy or induced pluripotent stem cells might be needed.…”

Section: Discussionmentioning

confidence: 99%

Genetic heterogeneity in Leigh syndrome: Highlighting treatable and novel genetic causes

et al. 2020

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Leigh syndrome (LS), the most common childhood mitochondrial disorder, has characteristic clinical and neuroradiologic features. Mutations in more than 75 genes have been identified in both the mitochondrial and nuclear genome, implicating a high degree of genetic heterogeneity in LS. To profile these genetic signatures and understand the pathophysiology of LS, we recruited 64 patients from 62 families who were clinically diagnosed with LS at Seoul National University Children's Hospital. Mitochondrial genetic analysis followed by whole‐exome sequencing was performed on 61 patients. Pathogenic variants in mitochondrial DNA were identified in 18 families and nuclear DNA mutations in 22. The following 17 genes analyzed in 40 families were found to have genetic complexity: MTATP6, MTND1, MTND3, MTND5, MTND6, MTTK, NDUFS1, NDUFV1, NDUFAF6, SURF1, SLC19A3, ECHS1, PNPT1, IARS2, NARS2, VPS13D, and NAXE. Two treatable cases had biotin‐thiamine responsive basal ganglia disease, and another three were identified as having defects in the newly recognized genes (VPS13D or NAXE). Variants in the nuclear genes that encoded mitochondrial aminoacyl tRNA synthetases were present in 27.3% of cases. Our findings expand the genetic and clinical spectrum of LS, showing genetic heterogeneity and highlighting treatable cases and those with novel genetic causes.

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Section: Discussionmentioning

confidence: 99%

Genetic heterogeneity in Leigh syndrome: Highlighting treatable and novel genetic causes

et al. 2020

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“…The ability of MSCs to modulate immune responses is considered as a safe and feasible strategy to treat Crohn's disease [98], systemic lupus erythematosus (SLE) [99,100], rheumatoid arthritis (RA) [101], GvHD [102], Type I diabetes [103] and so on. MSCs also prevent allergic airway inflammation and reduce the symptoms of severe asthma [104][105][106][107][108]. Administration of MSCs functionally attenuates airway hyper-responsiveness (AHR), inflammatory cell infiltration, and mucus production in animal models [104,[109][110][111][112][113].…”

Section: Therapeutic Properties Of Mscsmentioning

confidence: 99%

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

Fan

Zhang

et al. 2020

Cell. Mol. Life Sci.

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393

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Mesenchymal stem cells (MSCs) have been extensively investigated for the treatment of various diseases. The therapeutic potential of MSCs is attributed to complex cellular and molecular mechanisms of action including differentiation into multiple cell lineages and regulation of immune responses via immunomodulation. The plasticity of MSCs in immunomodulation allow these cells to exert different immune effects depending on different diseases. Understanding the biology of MSCs and their role in treatment is critical to determine their potential for various therapeutic applications and for the development of MSC-based regenerative medicine. This review summarizes the recent progress of particular mechanisms underlying the tissue regenerative properties and immunomodulatory effects of MSCs. We focused on discussing the functional roles of paracrine activities, direct cell-cell contact, mitochondrial transfer, and extracellular vesicles related to MSC-mediated effects on immune cell responses, cell survival, and regeneration. This will provide an overview of the current research on the rapid development of MSC-based therapies. Keywords Regenerative potential • Integration of MSCs • Immunomodulation • Soluble factors • Cell-cell contact • Mitochondrial transfer • Extracellular vesicles Abbreviations AHR Airway hyper-responsiveness Alix ALG-2-interacting protein X Ang-1 Angiopoietin-1 ASCs Adipose-derived stem cells BAX BCL-2-associated X protein BCL-2 B-cell lymphoma 2 CASP3 Caspase 3 CX43 Connexin 43 CXCR4 Chemokine receptor type 4 DC Dendritic cell Cellular and Molecular Life Sciences

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“…MSCs can promote macrophage differentiation to M2 phenotype contributing to the resolution of inflammation, and conversely, to M1 phenotype leading to augmented phagocytic activity [102,111]. Recent studies have demonstrated that MSCs can also transfer functional mitochondria to the damaged cells reducing oxidative stress in lung injury [112,113]. Keeping in view that oxidative stress-induced mitochondrial dysfunction can contribute to inflammation, transfer of mitochondria could be consider another anti-inflammatory effect of MSCs.…”

Section: Mesenchymal Stem Cells In Lung Inflammationmentioning

confidence: 99%

Lights and Shadows in the Use of Mesenchymal Stem Cells in Lung Inflammation, a Poorly Investigated Topic in Cystic Fibrosis

Caretti

Peli

Colombo

et al. 2019

Cells

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Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic stem cells residing in many tissues, including the lung. MSCs have long been regarded as a promising tool for cell-based therapy because of their ability to replace damaged tissue by differentiating into the resident cell and repopulating the injured area. Their ability to release soluble factors and extracellular vesicles has emerged as crucial in the resolution of inflammation and injury. There is a growing literature on the use of MSCs and MSC secretome to hamper inflammation in different lung pathologies, including: asthma, pneumonia, acute lung injury (ALI), pulmonary hypertension, and chronic obstructive pulmonary disease (COPD). However, their potential therapeutic role in the context of Cystic Fibrosis (CF) lung inflammation is still not fully characterized. CF morbidity and mortality are mainly due to progressive lung dysfunction. Lung inflammation is a chronic and unresolved condition that triggers progressive tissue damage. Thus, it becomes even more important to develop innovative immunomodulatory therapies aside from classic anti-inflammatory agents. Here, we address the main features of CF and the implications in lung inflammation. We then review how MSCs and MSC secretome participate in attenuating inflammation in pulmonary pathologies, emphasizing the significant potential of MSCs as new therapeutic approach in CF.

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Mesenchymal stem cells alleviate oxidative stress–induced mitochondrial dysfunction in the airways

Cited by 115 publications

References 40 publications

Genetic heterogeneity in Leigh syndrome: Highlighting treatable and novel genetic causes

Genetic heterogeneity in Leigh syndrome: Highlighting treatable and novel genetic causes

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

Lights and Shadows in the Use of Mesenchymal Stem Cells in Lung Inflammation, a Poorly Investigated Topic in Cystic Fibrosis

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