Absence of NUCKS augments paracrine effects of mesenchymal stem cells-mediated cardiac protection

Zhang, Yuelin; Chiu, Sin-Ming; Liang, Xiaoting; Chai, Yuet Hung; Qin, Yiming; Wang, Junwen; Li, Xiang; Qiu, Beiying; Tergaonkar, Vinay; Tse, Hung‐Fat; Lian, Qizhou

doi:10.1016/j.yexcr.2017.04.012

Cited by 18 publications

(16 citation statements)

References 41 publications

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“…Among the various types of stem cells currently used in pre-clinical and clinical trials, MSCs have been considered a favourable cell source for MI treatment because of their unique advantages, such as easy isolation, low immunogenicity and multipotent differentiation capacity. 20,22 However, most MSCs died within 3 days after transplantation in the harsh environment of the injured heart, thus limiting therapeutic efficacy. 23 Recently, accumulating evidence has demonstrated pharmacological pre-treatment as a novel strategy to promote the survival of transplanted BM-MSCs in the ischaemic heart.…”

Section: Discussionmentioning

confidence: 99%

Haemin pre‐treatment augments the cardiac protection of mesenchymal stem cells by inhibiting mitochondrial fission and improving survival

Deng

Liu

et al. 2019

J Cellular Molecular Medi

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The cardiac protection of mesenchymal stem cell (MSC) transplantation for myocardial infarction (MI) is largely hampered by low cell survival. Haem oxygenase 1 (HO‐1) plays a critical role in regulation of cell survival under many stress conditions. This study aimed to investigate whether pre‐treatment with haemin, a potent HO‐1 inducer, would promote the survival of MSCs under serum deprivation and hypoxia (SD/H) and enhance the cardioprotective effects of MSCs in MI. Bone marrow (BM)‐MSCs were pretreated with or without haemin and then exposed to SD/H. The mitochondrial morphology of MSCs was determined by MitoTracker staining. BM‐MSCs and haemin‐pretreated BM‐MSCs were transplanted into the peri‐infarct region in MI mice. SD/H induced mitochondrial fragmentation, as shown by increased mitochondrial fission and apoptosis of BM‐MSCs. Pre‐treatment with haemin greatly inhibited SD/H‐induced mitochondrial fragmentation and apoptosis of BM‐MSCs. These effects were partially abrogated by knocking down HO‐1. At 4 weeks after transplantation, compared with BM‐MSCs, haemin‐pretreated BM‐MSCs had greatly improved the heart function of mice with MI. These cardioprotective effects were associated with increased cell survival, decreased cardiomyocytes apoptosis and enhanced angiogenesis. Collectively, our study identifies haemin as a regulator of MSC survival and suggests a novel strategy for improving MSC‐based therapy for MI.

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Section: Discussionmentioning

confidence: 99%

Haemin pre‐treatment augments the cardiac protection of mesenchymal stem cells by inhibiting mitochondrial fission and improving survival

Deng

Liu

et al. 2019

J Cellular Molecular Medi

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“…Immunostaining was performed as previously described (18). The primary antibodies were anti-CD31 (ab7388; Abcam, Cambridge, United Kingdom) and anti-Troponin T (ab8295; Abcam); DAPI was used for nuclear counterstaining.…”

Section: Immunofluorescencementioning

confidence: 99%

Overexpression of ERBB4 rejuvenates aged mesenchymal stem cells and enhances angiogenesis via PI3K/AKT and MAPK/ERK pathways

et al. 2018

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The age‐related functional exhaustion limits potential efficacy of mesenchymal stem cells (MSC) in treating cardiovascular disease. Therefore, rejuvenation of aged MSC in the elderly population is of great interest. We have previously reported that Erb‐B2 receptor tyrosine kinase 4 (ERBB4) plays a critical role in regulating MSC survival under hypoxia. The aim of this study was to investigate whether ERBB4 rejuvenates aged MSC and how ERBB4 enhances therapeutic efficacy of aged MSC in treating myocardial infarction (MI). Compared with vector aged MSC (aged‐MSC), ERBB4‐engineered aged MSC (ER4‐aged‐MSC) conferred resistance to oxidative stress‐induced cell death and ameliorated the senescent phenotype in vitro. Four weeks after MI, the ER4‐aged‐MSC group exhibited enhanced blood vessel density, reduced cardiac remodeling and apoptosis with improved heart function compared with the aged‐MSC group. Overexpression of ERBB4 caused an increase in phosphorylated v‐akt murine thymoma viral oncogene homolog 1 (AKT), and phosphorylated ERK expression under hypoxia. ER4‐aged‐MSC secreted higher levels of angiopoietin, epithelial neutrophil activating peptide 78, VEGF, and fibroblast growth factor 2, and enhanced tube formation in HUVEC. The impact of ERBB4 on protein expression, proangiogenesis, cell behavior, and cytokine secretion was abolished by inhibiting PI3K/AKT and MAPK/ERK signaling pathway.—Liang, X., Ding, Y., Lin, F., Zhang, Y., Zhou, X., Meng, Q., Lu, X., Jiang, G., Zhu, H., Chen, Y., Lian, Q., Fan, H., Liu, Z. Overexpression of ERBB4 rejuvenates aged mesenchymal stem cells and enhances angiogenesis via PI3K/AKT and MAPK/ERK pathways. FASEB J. 33, 4559–4570 (2019). http://www.fasebj.org

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“…The paracrine effect of nuclear casein kinase on MSC and MSC-derived extracellular vesicles (EVs) has been studied [37]. The University of Cincinnati explored the cardiac protection mechanism of paracrine MSCs, which involves iPS cells (MiPS) [38], the Wnt11 signaling pathway [39], CXCR4 factor expression [40], the suicide gene [41] and the clusterin Akt/GATA-4 pathway [42].…”

Section: Discussionmentioning

confidence: 99%

Mapping Trends and Identifying Hotspots in Research on Mesenchymal Stem Cells in Cardiovascular Disease

Chen¹,

Lou²,

Lv³

et al. 2020

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Background: Mesenchymal stem cells (MSCs) have important research value and broad application prospects in the cardiovascular disease. This study in order to provide information on the latest progress, evolutionary path, frontier research hotspots and future research developmental trends in this field. Methods: A knowledge map was generated by CiteSpace and VOSviewer analysis software based on data obtained from the literature on MSCs in the cardiovascular field.Results: The USA and China ranked at the top in terms of the percentage of articles, accounting for 34.306% and 28.550%, respectively. The institution with the highest number of research publications in this field was the University of Miami, followed by the Chinese Academy of Medical Sciences and Harvard University. The research institution with the highest ACI value was Harvard University, followed by the Mayo Clinic and the University of Cincinnati.The top three subjects in terms of the number of published articles were cell biology, cardiovascular system cardiology and research experimental medicine. The journal with the most publications in this field was Circulation Research, followed by Scientific Reports and Biomaterials. The direction of research on MSCs in the cardiovascular system was divided into four parts: (1) tissue engineering and gene and material research, (2) cell transplantation and signal transduction pathway research, (3) assessment of the efficacy of the use of stem cells from different sources in the treatment of acute myocardial infarction, and (4) myocardial hypertrophy, heart failure and myocardial infarction regeneration and repair research. Tissue research is the hotspot and frontier in this field.Conclusion: MSC research has presented a gradual upward trend in the cardiovascular field. Multidisciplinary intersection is a characteristic of this field. Engineering and materials disciplines are particularly valued and have received attention from researchers. The progress in multidisciplinary research will provide motivation and technical support for the development of this field.

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Absence of NUCKS augments paracrine effects of mesenchymal stem cells-mediated cardiac protection

Cited by 18 publications

References 41 publications

Haemin pre‐treatment augments the cardiac protection of mesenchymal stem cells by inhibiting mitochondrial fission and improving survival

Haemin pre‐treatment augments the cardiac protection of mesenchymal stem cells by inhibiting mitochondrial fission and improving survival

Overexpression of ERBB4 rejuvenates aged mesenchymal stem cells and enhances angiogenesis via PI3K/AKT and MAPK/ERK pathways

Mapping Trends and Identifying Hotspots in Research on Mesenchymal Stem Cells in Cardiovascular Disease

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