Mesenchymal stem cells in acute lung injury: are they ready for translational medicine?

Xu, Feng; Hu, Yue; Zhou, Jiaxin; Wang, Xiangdong

doi:10.1111/jcmm.12063

Cited by 40 publications

(39 citation statements)

References 80 publications

(135 reference statements)

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“…Another possible explanation is the matter of age. Experiment on the animals show that the expression of the I Ca,L is decreased with aging [25]. Aging has also been related to decreased expressions of potassium and sodium channels [26, 27].…”

Section: Discussionmentioning

confidence: 99%

Novel trigenic CACNA1C/DES/MYPN mutations in a family of hypertrophic cardiomyopathy with early repolarization and short QT syndrome

et al. 2017

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BackgroundHypertrophic cardiomyopathy (HCM) patients with early repolarization (ER) pattern are at higher risk of ventricular arrhythmia, yet the genetic background of this situation has not been well investigated. Here we report novel trigenic mutations detected in a Chinese family of obstructive HCM with ER and short QT syndrome (SQTS).MethodsProband and family members underwent detailed medical assessments. DNAs were extracted from peripheral blood leukocytes for genetic screening with next generation method. The functional characterization of the mutation was conducted in TSA201 cells with patch-clamp experiment.ResultsThe proband was a 52-year-old male who had a ER pattern ECG in inferioral-lateral leads with atrioventricular block and QTc of 356 ms. He also suffered from severe left ventricular hypertrophy and dysfunction. Targeted sequencing revealed trigenic mutations: c.700G>A/p.E234K in DES, c.2966G>A/p.R989H in MYPN, and c.5918G>C/p.R1973P in CACNA1C. All mutations were also detected in his daughter with ER and mild myocardium hypertrophy. The CACNA1C-R1973P mutation caused significant reduction (68.4%) of ICa compared to CACNA1C-WT (n = 14 and 14, P < 0.05). The computer modeling showed that all 3 mutations were highly disease-causing. The proband received the CRT-D (cardiac resynchronizing therapy) implantation, which lowered the left ventricular outflow tract gradient (LVOTG, 124 mmHg pre vs. 27 mmHg post) and restored the LV function (LVEF 40% pre vs. 63% post).ConclusionsThe study reveals a novel CACNA1C mutation underlying the unique ER pattern ECGs with SQTS. It also shows the rare trigenic mutations are the pathogenic substrates for the complicated clinical manifestation in HCM patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-017-1180-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Novel trigenic CACNA1C/DES/MYPN mutations in a family of hypertrophic cardiomyopathy with early repolarization and short QT syndrome

et al. 2017

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“…Regenerative medicine using human stem cells is a novel strategy for the treatment of various intractable diseases and damaged organs, including difficult-to-treat lung diseases [1]. Many studies have demonstrated that bone marrow-derived mesenchymal stem cells (BM-MSCs) appear to exert anti-inflammation and anti-apoptosis effects and represent a promising field for the treatment of acute lung injury (ALI) and acute respiratory distress syndrome [2,3].…”

Section: Introductionmentioning

confidence: 99%

Bone marrow‐derived mesenchymal stem cells enhance autophagy via PI3K/AKT signalling to reduce the severity of ischaemia/reperfusion‐induced lung injury

Zhou

Zhang

et al. 2015

J Cellular Molecular Medi

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Autophagy, a type II programmed cell death, is essential for cell survival under stress, e.g. lung injury, and bone marrow-derived mesenchymal stem cells (BM-MSCs) have great potential for cell therapy. However, the mechanisms underlying the BM-MSC activation of autophagy to provide a therapeutic effect in ischaemia/reperfusion-induced lung injury (IRI) remain unclear. Thus, we investigate the activation of autophagy in IRI following transplantation with BM-MSCs. Seventy mice were pre-treated with BM-MSCs before they underwent lung IRI surgery in vivo. Human pulmonary micro-vascular endothelial cells (HPMVECs) were pre-conditioned with BM-MSCs by oxygen-glucose deprivation/reoxygenation (OGD) in vitro. Expression markers for autophagy and the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signalling pathway were analysed. In IRI-treated mice, administration of BM-MSCs significantly attenuated lung injury and inflammation, and increased the level of autophagy. In OGD-treated HPMVECs, co-culture with BM-MSCs attenuated endothelial permeability by decreasing the level of cell death and enhanced autophagic activation. Moreover, administration of BM-MSCs decreased the level of PI3K class I and p-Akt while the expression of PI3K class III was increased. Finally, BM-MSCs-induced autophagic activity was prevented using the inhibitor LY294002. Administration of BM-MSCs attenuated lung injury by improving the autophagy level via the PI3K/Akt signalling pathway. These findings provide further understanding of the mechanisms related to BM-MSCs and will help to develop new cell-based therapeutic strategies in lung injury.

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“…In response to inflammation or tissue injury, MSCs are able to differentiate into various cells of the mesenchymal lineage and to engraft into many tissues, where they promote tissue repair . In a model of DSS‐induced rat colitis, intravenously administered rat MSCs migrated to the lamina propria of the injured colon, where they upregulated their expression of α‐smooth muscle actin (α‐SMA), and were able to heal epithelial injuries.…”

Section: Properties Of Mscsmentioning

confidence: 99%

“…In response to inflammation or tissue injury, MSCs are able to differentiate into various cells of the mesenchymal lineage and to engraft into many tissues, [80][81][82] where they promote tissue repair. [83][84][85][86][87][88][89] In a model of DSS-induced rat colitis, intravenously administered rat MSCs migrated to the lamina propria of the injured colon, where they upregulated their expression of a-smooth muscle actin (a-SMA), and were able to heal epithelial injuries. However, tissue repair properties of MSCs are not so much due to their differentiation capacities, but rather to their ability to stimulate survival and recovery of local tissues, through stimulation of angiogenesis and inhibition of apoptosis and fibrosis in injured tissues.…”

Section: Tissue Regenerationmentioning

confidence: 99%

Review article: mesenchymal stromal cell therapy for inflammatory bowel diseases

Gregoire

Lechanteur²,

Briquet³

et al. 2016

Aliment Pharmacol Ther

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Mesenchymal stem cells in acute lung injury: are they ready for translational medicine?

Cited by 40 publications

References 80 publications

Novel trigenic CACNA1C/DES/MYPN mutations in a family of hypertrophic cardiomyopathy with early repolarization and short QT syndrome

Novel trigenic CACNA1C/DES/MYPN mutations in a family of hypertrophic cardiomyopathy with early repolarization and short QT syndrome

Bone marrow‐derived mesenchymal stem cells enhance autophagy via PI3K/AKT signalling to reduce the severity of ischaemia/reperfusion‐induced lung injury

Review article: mesenchymal stromal cell therapy for inflammatory bowel diseases

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