Combining stem cells in myocardial infarction: The road to superior repair?

Beliën, Hanne; Evens, L; Hendrikx, Marc; Bito, Virginie; Bronckaers, Annelies

doi:10.1002/med.21839

Cited by 26 publications

(17 citation statements)

References 171 publications

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“…Over the past few decades, enthusiastic attempts have been made to improve post-infarction prognosis in MI by targeting signaling pathways, which are known as emerging therapies, including pharmacotherapy, gene therapy, protein therapy, cell therapy, and exosome therapy 12,20,21 . These therapies address the essential causes of MI progression by targeting key signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

Signaling pathways and targeted therapy for myocardial infarction

Zhang

Wang

et al. 2022

Sig Transduct Target Ther

211

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: Introductionmentioning

confidence: 99%

Signaling pathways and targeted therapy for myocardial infarction

Zhang

Wang

et al. 2022

Sig Transduct Target Ther

211

117

View full text Add to dashboard Cite

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“…Stem cell therapy is a promising strategy for augmenting myocardial repair, but its clinical use is highly restricted by the low retention and poor survival of engrafted cells. In recent years, novel strategies, including MSCs modifications and combining cell therapy, have been developed to enhance the efficacy of stemcell-based therapy [ 68 , 69 ]. In this study, we found that sequential transplantation of exosomes and combinatorially pretreated MSCs further facilitated cardiac recovery.…”

Section: Discussionmentioning

confidence: 99%

Sequential transplantation of exosomes and mesenchymal stem cells pretreated with a combination of hypoxia and Tongxinluo efficiently facilitates cardiac repair

Xiong

Tang

et al. 2022

Stem Cell Res Ther

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Background Bone marrow-derived mesenchymal stem cells (MSCs), which possess immunomodulatory characteristic, are promising candidates for the treatment of acute myocardial infarction (AMI). However, the low retention and survival rate of MSCs in the ischemic heart limit their therapeutic efficacy. Strategies either modifying MSCs or alleviating the inflammatory environment, which facilitates the recruitment and survival of the engrafted MSCs, may solve the problem. Thus, we aimed to explore the therapeutic efficacy of sequential transplantation of exosomes and combinatorial pretreated MSCs in the treatment of AMI. Methods Exosomes derived from MSCs were delivered to infarcted hearts through intramyocardial injection followed by the intravenous infusion of differentially pretreated MSCs on Day 3 post-AMI. Enzyme linked immunosorbent assay (ELISA) was performed to evaluate the inflammation level as well as the SDF-1 levels in the infarcted border zone of the heart. Echocardiography and histological analysis were performed to assess cardiac function, infarct size, collagen area and angiogenesis. Results Sequential transplantation of exosomes and the combinatorial pretreated MSCs significantly facilitated cardiac repair compared to AMI rats treated with exosomes alone. Notably, compared to the other three methods of cotransplantation, combinatorial pretreatment with hypoxia and Tongxinluo (TXL) markedly enhanced the CXCR4 level of MSCs and promoted recruitment, which resulted in better cardiac function, smaller infarct size and enhanced angiogenesis. We further demonstrated that exosomes effectively reduced apoptosis in MSCs in vitro. Conclusion Sequential delivery of exosomes and pretreated MSCs facilitated cardiac repair post-AMI, and combined pretreatment with hypoxia and TXL better enhanced the cardioprotective effects. This method provides new insight into the clinical translation of stem cell-based therapy for AMI.

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“…Especially, myocardial infarction, one of the representative CVD and the leading causes of mortality worldwide, is caused by acute or persistent ischemia and hypoxia of coronary artery, resulting in subsequent cell apoptosis and cardiac dysfunction. With the purpose of restoring cardiomyocytes, stem cell-based treatments have been extensively implemented for MI in the past years 168 - 170 . More attractively, numerous preclinical studies have found that the MSC-EVs have the similar myocardial regeneration functions with their donor cells via proliferation of the cardiomyocytes, inhibition of cardiac cell apoptosis, pro-angiogenesis, and reduction of infarct size 171 .…”

Section: Tissue Regeneration Applications Of Evs On Various Organsmentioning

confidence: 99%

Extracellular vesicles as bioactive nanotherapeutics: An emerging paradigm for regenerative medicine

Fang

Sun

et al. 2022

Theranostics

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In recent decades, extracellular vesicles (EVs), as bioactive cell-secreted nanoparticles which are involved in various physiological and pathological processes including cell proliferation, immune regulation, angiogenesis and tissue repair, have emerged as one of the most attractive nanotherapeutics for regenerative medicine. Herein we provide a systematic review of the latest progress of EVs for regenerative applications. Firstly, we will briefly introduce the biogenesis, function and isolation technology of EVs. Then, the underlying therapeutic mechanisms of the native unmodified EVs and engineering strategies of the modified EVs as regenerative entities will be discussed. Subsequently, the main focus will be placed on the tissue repair and regeneration applications of EVs on various organs including brain, heart, bone and cartilage, liver and kidney, as well as skin. More importantly, current clinical trials of EVs for regenerative medicine will also be briefly highlighted. Finally, the future challenges and insightful perspectives of the currently developed EV-based nanotherapeutics in biomedicine will be discussed. In short, the bioactive EV-based nanotherapeutics have opened new horizons for biologists, chemists, nanoscientists, pharmacists, as well as clinicians, making possible powerful tools and therapies for regenerative medicine.

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Combining stem cells in myocardial infarction: The road to superior repair?

Cited by 26 publications

References 171 publications

Signaling pathways and targeted therapy for myocardial infarction

Signaling pathways and targeted therapy for myocardial infarction

Sequential transplantation of exosomes and mesenchymal stem cells pretreated with a combination of hypoxia and Tongxinluo efficiently facilitates cardiac repair

Extracellular vesicles as bioactive nanotherapeutics: An emerging paradigm for regenerative medicine

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