TMSB4 Overexpression Enhances the Potency of Marrow Mesenchymal Stromal Cells for Myocardial Repair

Tang, Shiyuan; Fan, Chengming; Iroegbu, Chukwuemeka Daniel; Zhou, Wenwu; Zhang, Zhigong; Wu, Ming; Chen, Wang‐Ping; Wu, Xiaoming; Peng, Jun; Li, Zhihong; Yang, Jinfu

doi:10.3389/fcell.2021.670913

Cited by 7 publications

(7 citation statements)

References 23 publications

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“…Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and thymosin β4 microspheres were simultaneously injected into pigs after MI induction, and the microspheres delivered thymosin β4 to improve the engraftment and reparative properties of stem cells post-transplantation by heightening Akt activity 93 . In addition, relying on activation of the Akt pathway, nerve growth factor nanoparticles enhanced the therapeutic potency of human umbilical cord mesenchymal stem cells (hUCMSCs) 94 and paracrine effects on Akt-modified BMMSC-mediated cardiac protection and functional improvement 92,95 , similar to the cardioprotective effects of edaravone-treated 96 , EGb761-treated 97 TMSB4-transfected 98 or IP6K-inhibited 99 BMMSCs and rosuvastatin-supplemented adiposederived stem cells (ADSCs) 100 .…”

Section: Pi3k/akt Pathway In MImentioning

confidence: 99%

Signaling pathways and targeted therapy for myocardial infarction

Zhang

Wang

et al. 2022

Sig Transduct Target Ther

277

117

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Although the treatment of myocardial infarction (MI) has improved considerably, it is still a worldwide disease with high morbidity and high mortality. Whilst there is still a long way to go for discovering ideal treatments, therapeutic strategies committed to cardioprotection and cardiac repair following cardiac ischemia are emerging. Evidence of pathological characteristics in MI illustrates cell signaling pathways that participate in the survival, proliferation, apoptosis, autophagy of cardiomyocytes, endothelial cells, fibroblasts, monocytes, and stem cells. These signaling pathways include the key players in inflammation response, e.g., NLRP3/caspase-1 and TLR4/MyD88/NF-κB; the crucial mediators in oxidative stress and apoptosis, for instance, Notch, Hippo/YAP, RhoA/ROCK, Nrf2/HO-1, and Sonic hedgehog; the controller of myocardial fibrosis such as TGF-β/SMADs and Wnt/β-catenin; and the main regulator of angiogenesis, PI3K/Akt, MAPK, JAK/STAT, Sonic hedgehog, etc. Since signaling pathways play an important role in administering the process of MI, aiming at targeting these aberrant signaling pathways and improving the pathological manifestations in MI is indispensable and promising. Hence, drug therapy, gene therapy, protein therapy, cell therapy, and exosome therapy have been emerging and are known as novel therapies. In this review, we summarize the therapeutic strategies for MI by regulating these associated pathways, which contribute to inhibiting cardiomyocytes death, attenuating inflammation, enhancing angiogenesis, etc. so as to repair and re-functionalize damaged hearts.

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Section: Pi3k/akt Pathway In MImentioning

confidence: 99%

Signaling pathways and targeted therapy for myocardial infarction

Zhang

Wang

et al. 2022

Sig Transduct Target Ther

277

117

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show abstract

“…Angiogenesis, the formation of new blood vessels from preexisting ones, is indispensable for revascularization and cardiac remodeling following MI ( Mathiyalagan et al, 2019 ; Chong et al, 2021 ; Tang et al, 2021 ). Ischemic heart disease is a leading cause of mortality and results from vascular cavity stenosis and occlusion ( Garry et al, 2021 ).…”

Section: Effects Of Berberine On Vascular Diseasesmentioning

confidence: 99%

Berberine: A Review of its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases

Peng

et al. 2021

Front. Pharmacol.

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Traditional Chinese medicine plays a significant role in the treatment of various diseases and has attracted increasing attention for clinical applications. Vascular diseases affecting vasculature in the heart, cerebrovascular disease, atherosclerosis, and diabetic complications have compromised quality of life for affected individuals and increase the burden on health care services. Berberine, a naturally occurring isoquinoline alkaloid form Rhizoma coptidis, is widely used in China as a folk medicine for its antibacterial and anti-inflammatory properties. Promisingly, an increasing number of studies have identified several cellular and molecular targets for berberine, indicating its potential as an alternative therapeutic strategy for vascular diseases, as well as providing novel evidence that supports the therapeutic potential of berberine to combat vascular diseases. The purpose of this review is to comprehensively and systematically describe the evidence for berberine as a therapeutic agent in vascular diseases, including its pharmacological effects, molecular mechanisms, and pharmacokinetics. According to data published so far, berberine shows remarkable anti-inflammatory, antioxidant, antiapoptotic, and antiautophagic activity via the regulation of multiple signaling pathways, including AMP-activated protein kinase (AMPK), nuclear factor κB (NF-κB), mitogen-activated protein kinase silent information regulator 1 (SIRT-1), hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), janus kinase 2 (JAK-2), Ca2+ channels, and endoplasmic reticulum stress. Moreover, we discuss the existing limitations of berberine in the treatment of vascular diseases, and give corresponding measures. In addition, we propose some research perspectives and challenges, and provide a solid evidence base from which further studies can excavate novel effective drugs from Chinese medicine monomers.

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“… 45 So, we employed intramyocardial injection instead of intracoronary injection, in order to achieve better efficacy of CPPs‐Exo on injured heart. Moreover, there are emerging combination therapies for MI, such as cell therapy combined with gene therapy, 46 or pharmacotherapy, 47 or protein therapy, 48 or exosome therapy plus gene therapy, 49 which provide new directions for the future research on CPPs.…”

Section: Discussionmentioning

confidence: 99%

Cardiopulmonary progenitors facilitate cardiac repair via exosomal transfer of miR‐27b‐3p targeting the SIK1‐CREB1 axis

Xiao,

Xia,

Jiang

et al. 2024

Cell Proliferation

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Ischemic heart disease, especially myocardial infarction (MI), is one of the leading causes of death worldwide, and desperately needs effective treatments, such as cell therapy. Cardiopulmonary progenitors (CPPs) are stem cells for both heart and lung, but their repairing role in damaged heart is still unknown. Here, we obtained CPPs from E9.5 mouse embryos, maintained their stemness while expanding, and identified their characteristics by scRNA‐seq, flow cytometry, quantitative reverse transcription‐polymerase chain reaction, and differentiation assays. Moreover, we employed mouse MI model to investigate whether CPPs could repair the injured heart. Our data identified that CPPs exhibit hybrid fibroblastic, endothelial, and mesenchymal state, and they could differentiate into cell lineages within the cardiopulmonary system. Moreover, intramyocardial injection of CPPs improves cardiac function through CPPs exosomes (CPPs‐Exo) by promotion of cardiomyocytic proliferation and vascularization. To uncover the underlying mechanism, we used miRNA‐seq, bulk RNA‐seq, and bioinformatic approaches, and found the highly expressed miR‐27b‐3p in CPPs‐Exo and its target gene Sik1, which can influence the transcriptional activity of CREB1. Therefore, we postulate that CPPs facilitate cardiac repair partially through the SIK1‐CREB1 axis via exosomal miR‐27b‐3p. Our study offers a novel insight into the role of CPPs‐Exo in heart repair and highlights the potential of CPPs‐Exo as a promising therapeutic strategy for MI.

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TMSB4 Overexpression Enhances the Potency of Marrow Mesenchymal Stromal Cells for Myocardial Repair

Cited by 7 publications

References 23 publications

Signaling pathways and targeted therapy for myocardial infarction

Signaling pathways and targeted therapy for myocardial infarction

Berberine: A Review of its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases

Cardiopulmonary progenitors facilitate cardiac repair via exosomal transfer of miR‐27b‐3p targeting the SIK1‐CREB1 axis

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