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Article ; Online: Cardiac Cell Therapy for Heart Repair: Should the Cells Be Left Out?

Zhu, Dashuai / Cheng, Ke

2021 Volume 10, Issue 3

Abstract: Cardiovascular disease (CVD) is still the leading cause of death worldwide. Coronary artery occlusion, or myocardial infarction (MI) causes massive loss of cardiomyocytes. The ischemia area is eventually replaced by a fibrotic scar. From the mechanical ... ...

Abstract	Cardiovascular disease (CVD) is still the leading cause of death worldwide. Coronary artery occlusion, or myocardial infarction (MI) causes massive loss of cardiomyocytes. The ischemia area is eventually replaced by a fibrotic scar. From the mechanical dysfunctions of the scar in electronic transduction, contraction and compliance, pathological cardiac dilation and heart failure develops. Once end-stage heart failure occurs, the only option is to perform heart transplantation. The sequential changes are termed cardiac remodeling, and are due to the lack of endogenous regenerative actions in the adult human heart. Regenerative medicine and biomedical engineering strategies have been pursued to repair the damaged heart and to restore normal cardiac function. Such strategies include both cellular and acellular products, in combination with biomaterials. In addition, substantial progress has been made to elucidate the molecular and cellular mechanisms underlying heart repair and regeneration. In this review, we summarize and discuss current therapeutic approaches for cardiac repair and provide a perspective on novel strategies that holding potential opportunities for future research and clinical translation.
MeSH term(s)	Cell- and Tissue-Based Therapy/methods ; Heart Failure/pathology ; Heart Failure/therapy ; Humans ; Myocardium/pathology ; Myocytes, Cardiac/metabolism ; Tissue Engineering/methods
Language	English
Publishing date	2021-03-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10030641
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Detachable Microneedle Patches Deliver Mesenchymal Stromal Cell Factor-Loaded Nanoparticles for Cardiac Repair.

Hu, Shiqi / Zhu, Dashuai / Li, Zhenhua / Cheng, Ke

ACS nano

2022 Volume 16, Issue 10, Page(s) 15935–15945

Abstract: Intramyocardial injection is a direct and efficient approach to deliver therapeutics to the heart. However, the injected volume must be very limited, and there is injury to the injection site and leakage issues during heart beating. Herein, we developed ... ...

Abstract	Intramyocardial injection is a direct and efficient approach to deliver therapeutics to the heart. However, the injected volume must be very limited, and there is injury to the injection site and leakage issues during heart beating. Herein, we developed a detachable therapeutic microneedle (MN) patch, which is comprised of mesenchymal stromal cell-secreted factors (MSCF)-loaded poly(lactic-
MeSH term(s)	Animals ; Rats ; Elastin ; Polylactic Acid-Polyglycolic Acid Copolymer ; Hyaluronic Acid ; Mesenchymal Stem Cells ; Myocytes, Cardiac ; Myocardium ; Nanoparticles ; Peptides
Chemical Substances	Elastin (9007-58-3) ; Polylactic Acid-Polyglycolic Acid Copolymer (1SIA8062RS) ; Hyaluronic Acid (9004-61-9) ; Peptides
Language	English
Publishing date	2022-09-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1936-086X
ISSN (online)	1936-086X
DOI	10.1021/acsnano.2c03060
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Article ; Online: Minimally invasive delivery of a hydrogel-based exosome patch to prevent heart failure.

Cheng, George / Zhu, Dashuai / Huang, Ke / Caranasos, Thomas G

Journal of molecular and cellular cardiology

2022 Volume 169, Page(s) 113–121

Abstract: Coronary heart disease (CHD) has been the number one killer in the United States for decades and causes millions of deaths each year. Clinical treatment of heart ischemic injury relieves symptoms in the acute stage of CHD; however, patients with an ... ...

Abstract	Coronary heart disease (CHD) has been the number one killer in the United States for decades and causes millions of deaths each year. Clinical treatment of heart ischemic injury relieves symptoms in the acute stage of CHD; however, patients with an infarcted heart muscle can develop heart failure (HF) due to chronic maladaptive remodeling. Regenerative therapy has been studied as a potential treatment option for myocardial infarction (MI) and HF. Cardiac patches have been designed and tested to increase therapeutic retention and integration. However, the delivery usually requires invasive surgical techniques, including open-chest surgeries and heart manipulation. Those procedures may cause chronic adhesions between the heart anterior wall and the chest wall. This study created and tested an injectable ExoGel by embedding mesenchymal stem cell (MSC) -derived exosomes into a hyaluronic acid (HA) hydrogel. ExoGel was injected into the pericardial cavity of rats with transverse aortic constriction (TAC) induced heart failure. ExoGel therapy reduced LV chamber size and preserved wall thickness. The feasibility and safety of ExoGel injection were further confirmed in a pig model.
MeSH term(s)	Animals ; Exosomes ; Heart Failure ; Hydrogels/therapeutic use ; Myocardial Infarction/drug therapy ; Myocardium ; Rats ; Swine
Chemical Substances	Hydrogels
Language	English
Publishing date	2022-06-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80157-4
ISSN	1095-8584 ; 0022-2828
ISSN (online)	1095-8584
ISSN	0022-2828
DOI	10.1016/j.yjmcc.2022.04.020
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Article: Bioengineering Technologies for Cardiac Regenerative Medicine.

Chingale, Mira / Zhu, Dashuai / Cheng, Ke / Huang, Ke

Frontiers in bioengineering and biotechnology

2021 Volume 9, Page(s) 681705

Abstract: Cardiac regenerative medicine faces big challenges such as a lack of adult cardiac stem cells, low turnover of mature cardiomyocytes, and difficulty in therapeutic delivery to the injured heart. The interaction of bioengineering and cardiac regenerative ... ...

Abstract	Cardiac regenerative medicine faces big challenges such as a lack of adult cardiac stem cells, low turnover of mature cardiomyocytes, and difficulty in therapeutic delivery to the injured heart. The interaction of bioengineering and cardiac regenerative medicine offers innovative solutions to this field. For example, cell reprogramming technology has been applied by both direct and indirect routes to generate patient-specific cardiomyocytes. Various viral and non-viral vectors have been utilized for gene editing to intervene gene expression patterns during the cardiac remodeling process. Cell-derived protein factors, exosomes, and miRNAs have been isolated and delivered through engineered particles to overcome many innate limitations of live cell therapy. Protein decoration, antibody modification, and platelet membranes have been used for targeting and precision medicine. Cardiac patches have been used for transferring therapeutics with better retention and integration. Other technologies such as 3D printing and 3D culture have been used to create replaceable cardiac tissue. In this review, we discuss recent advancements in bioengineering and biotechnologies for cardiac regenerative medicine.
Language	English
Publishing date	2021-06-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2719493-0
ISSN	2296-4185
ISSN	2296-4185
DOI	10.3389/fbioe.2021.681705
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Article: Comparison of extruded cell nanovesicles and exosomes in their molecular cargos and regenerative potentials.

Wang, Xianyun / Hu, Shiqi / Zhu, Dashuai / Li, Junlang / Cheng, Ke / Liu, Gang

Nano research

2023 Volume 16, Issue 5, Page(s) 7248–7259

Abstract: Extracellular vesicles (EVs) generated from mesenchymal stem cells (MSCs) play an essential role in modulating cell-cell communication and tissue regeneration. The clinical translation of EVs is constrained by the poor yield of EVs. Extrusion has ... ...

Abstract	Extracellular vesicles (EVs) generated from mesenchymal stem cells (MSCs) play an essential role in modulating cell-cell communication and tissue regeneration. The clinical translation of EVs is constrained by the poor yield of EVs. Extrusion has recently become an effective technique for producing a large scale of nanovesicles (NVs). In this study, we systematically compared MSC NVs (from extrusion) and EVs (from natural secretion). Proteomics and RNA sequencing data revealed that NVs resemble MSCs more closely than EVs. Additionally, microRNAs in NVs are related to cardiac repair, fibrosis repression, and angiogenesis. Lastly, intravenous delivery of MSC NVs improved heart repair and cardiac function in a mouse model of myocardial infarction. Electronic supplementary material: Supplementary material (Figs. S1-S4) is available in the online version of this article at 10.1007/s12274-023-5374-3.
Language	English
Publishing date	2023-02-28
Publishing country	China
Document type	Journal Article
ZDB-ID	2442216-2
ISSN	1998-0000 ; 1998-0124
ISSN (online)	1998-0000
ISSN	1998-0124
DOI	10.1007/s12274-023-5374-3
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Article ; Online: Intrapericardial long non-coding RNA-Tcf21 antisense RNA inducing demethylation administration promotes cardiac repair.

Zhu, Dashuai / Liu, Shuo / Huang, Ke / Li, Junlang / Mei, Xuan / Li, Zhenhua / Cheng, Ke

European heart journal

2023 Volume 44, Issue 19, Page(s) 1748–1760

Abstract: Aims: Epicardium and epicardium-derived cells are critical players in myocardial fibrosis. Mesenchymal stem cell-derived extracellular vesicles (EVs) have been studied for cardiac repair to improve cardiac remodelling, but the actual mechanisms remain ... ...

Abstract	Aims: Epicardium and epicardium-derived cells are critical players in myocardial fibrosis. Mesenchymal stem cell-derived extracellular vesicles (EVs) have been studied for cardiac repair to improve cardiac remodelling, but the actual mechanisms remain elusive. The aim of this study is to investigate the mechanisms of EV therapy for improving cardiac remodelling and develop a promising treatment addressing myocardial fibrosis. Methods and results: Extracellular vesicles were intrapericardially injected for mice myocardial infarction treatment. RNA-seq, in vitro gain- and loss-of-function experiments, and in vivo studies were performed to identify targets that can be used for myocardial fibrosis treatment. Afterward, a lipid nanoparticle-based long non-coding RNA (lncRNA) therapy was prepared for mouse and porcine models of myocardial infarction treatment. Intrapericardial injection of EVs improved adverse myocardial remodelling in mouse models of myocardial infarction. Mechanistically, Tcf21 was identified as a potential target to improve cardiac remodelling. Loss of Tcf21 function in epicardium-derived cells caused increased myofibroblast differentiation, whereas forced Tcf21 overexpression suppressed transforming growth factor-β signalling and myofibroblast differentiation. LncRNA-Tcf21 antisense RNA inducing demethylation (TARID) that enriched in EVs was identified to up-regulate Tcf21 expression. Formulated lncRNA-TARID-laden lipid nanoparticles up-regulated Tcf21 expression in epicardium-derived cells and improved cardiac function and histology in mouse and porcine models of myocardial infarction. Conclusion: This study identified Tcf21 as a critical target for improving cardiac fibrosis. Up-regulating Tcf21 by using lncRNA-TARID-laden lipid nanoparticles could be a promising way to treat myocardial fibrosis. This study established novel mechanisms underlying EV therapy for improving adverse remodelling and proposed a lncRNA therapy for cardiac fibrosis.
MeSH term(s)	Mice ; Animals ; Swine ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; RNA, Antisense/genetics ; RNA, Antisense/metabolism ; Ventricular Remodeling ; Myocardial Infarction/genetics ; Myocardial Infarction/therapy ; Myocardial Infarction/metabolism ; Fibrosis ; Demethylation
Chemical Substances	RNA, Long Noncoding ; RNA, Antisense
Language	English
Publishing date	2023-03-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	603098-1
ISSN	1522-9645 ; 0195-668X
ISSN (online)	1522-9645
ISSN	0195-668X
DOI	10.1093/eurheartj/ehad114
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Zs.A 1563: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 640: Show issues

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Article ; Online: A SARS-CoV-2 and influenza double hit vaccine based on RBD-conjugated inactivated influenza A virus.

Wang, Zhenzhen / Li, Zhenhua / Shi, Weiwei / Zhu, Dashuai / Hu, Shiqi / Dinh, Phuong-Uyen C / Cheng, Ke

Science advances

2023 Volume 9, Issue 25, Page(s) eabo4100

Abstract: The circulating flu viruses merging with the ongoing COVID-19 pandemic raises a more severe threat that promotes the infectivity of SARS-CoV-2 associated with higher mortality rates. Here, we conjugated recombinant receptor binding domain (RBD) of SARS- ... ...

Abstract	The circulating flu viruses merging with the ongoing COVID-19 pandemic raises a more severe threat that promotes the infectivity of SARS-CoV-2 associated with higher mortality rates. Here, we conjugated recombinant receptor binding domain (RBD) of SARS-CoV-2 spike protein onto inactivated influenza A virus (Flu) to develop a SARS-CoV-2 virus-like particle (VLP) vaccine with two-hit protection. This double-hit vaccine (Flu-RBD) not only induced protective immunities against SARS-CoV-2 but also remained functional as a flu vaccine. The Flu core improved the retention and distribution of Flu-RBD vaccine in the draining lymph nodes, with enhanced immunogenicity. In a hamster model of live SARS-CoV-2 infection, two doses of Flu-RBD efficiently protected animals against viral infection. Furthermore, Flu-RBD VLP elicited a strong neutralization activity against both SARS-CoV-2 Delta pseudovirus and wild-type influenza A H1N1 inactivated virus in mice. Overall, the Flu-RBD VLP vaccine is a promising candidate for combating COVID-19, influenza A, and coinfection.
MeSH term(s)	Cricetinae ; Animals ; Humans ; Mice ; Influenza Vaccines ; SARS-CoV-2 ; Influenza, Human ; Influenza A Virus, H1N1 Subtype ; Pandemics ; COVID-19/prevention & control ; COVID-19 Vaccines ; Influenza A virus
Chemical Substances	Influenza Vaccines ; spike protein, SARS-CoV-2 ; COVID-19 Vaccines
Language	English
Publishing date	2023-06-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.abo4100
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Article ; Online: An inhaled bioadhesive hydrogel to shield non-human primates from SARS-CoV-2 infection.

Mei, Xuan / Li, Junlang / Wang, Zhenzhen / Zhu, Dashuai / Huang, Ke / Hu, Shiqi / Popowski, Kristen D / Cheng, Ke

Nature materials

2023 Volume 22, Issue 7, Page(s) 903–912

Abstract: The surge of fast-spreading SARS-CoV-2 mutated variants highlights the need for fast, broad-spectrum strategies to counteract viral infections. In this work, we report a physical barrier against SARS-CoV-2 infection based on an inhalable bioadhesive ... ...

Abstract	The surge of fast-spreading SARS-CoV-2 mutated variants highlights the need for fast, broad-spectrum strategies to counteract viral infections. In this work, we report a physical barrier against SARS-CoV-2 infection based on an inhalable bioadhesive hydrogel, named spherical hydrogel inhalation for enhanced lung defence (SHIELD). Conveniently delivered via a dry powder inhaler, SHIELD particles form a dense hydrogel network that coats the airway, enhancing the diffusional barrier properties and restricting virus penetration. SHIELD's protective effect is first demonstrated in mice against two SARS-CoV-2 pseudo-viruses with different mutated spike proteins. Strikingly, in African green monkeys, a single SHIELD inhalation provides protection for up to 8 hours, efficiently reducing infection by the SARS-CoV-2 WA1 and B.1.617.2 (Delta) variants. Notably, SHIELD is made with food-grade materials and does not affect normal respiratory functions. This approach could offer additional protection to the population against SARS-CoV-2 and other respiratory pathogens.
MeSH term(s)	Animals ; Chlorocebus aethiops ; Mice ; COVID-19 ; SARS-CoV-2 ; Hydrogels ; Primates
Chemical Substances	Hydrogels
Language	English
Publishing date	2023-02-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2088679-2
ISSN	1476-4660 ; 1476-1122
ISSN (online)	1476-4660
ISSN	1476-1122
DOI	10.1038/s41563-023-01475-7
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Article ; Online: Inhalation of ACE2-expressing lung exosomes provides prophylactic protection against SARS-CoV-2.

Wang, Zhenzhen / Hu, Shiqi / Popowski, Kristen D / Liu, Shuo / Zhu, Dashuai / Mei, Xuan / Li, Junlang / Hu, Yilan / Dinh, Phuong-Uyen C / Wang, Xiaojie / Cheng, Ke

Nature communications

2024 Volume 15, Issue 1, Page(s) 2236

Abstract: Continued emergence of SARS-CoV-2 variants of concern that are capable of escaping vaccine-induced immunity highlights the urgency of developing new COVID-19 therapeutics. An essential mechanism for SARS-CoV-2 infection begins with the viral spike ... ...

Abstract	Continued emergence of SARS-CoV-2 variants of concern that are capable of escaping vaccine-induced immunity highlights the urgency of developing new COVID-19 therapeutics. An essential mechanism for SARS-CoV-2 infection begins with the viral spike protein binding to the human ACE2. Consequently, inhibiting this interaction becomes a highly promising therapeutic strategy against COVID-19. Herein, we demonstrate that ACE2-expressing human lung spheroid cells (LSC)-derived exosomes (LSC-Exo) could function as a prophylactic agent to bind and neutralize SARS-CoV-2, protecting the host against SARS-CoV-2 infection. Inhalation of LSC-Exo facilitates its deposition and biodistribution throughout the whole lung in a female mouse model. We show that LSC-Exo blocks the interaction of SARS-CoV-2 with host cells in vitro and in vivo by neutralizing the virus. LSC-Exo treatment protects hamsters from SARS-CoV-2-induced disease and reduced viral loads. Furthermore, LSC-Exo intercepts the entry of multiple SARS-CoV-2 variant pseudoviruses in female mice and shows comparable or equal potency against the wild-type strain, demonstrating that LSC-Exo may act as a broad-spectrum protectant against existing and emerging virus variants.
MeSH term(s)	Cricetinae ; Female ; Animals ; Humans ; Mice ; SARS-CoV-2 ; COVID-19 ; Angiotensin-Converting Enzyme 2 ; Exosomes ; Tissue Distribution ; Spike Glycoprotein, Coronavirus ; Antibodies, Neutralizing
Chemical Substances	Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Spike Glycoprotein, Coronavirus ; Antibodies, Neutralizing ; spike protein, SARS-CoV-2
Language	English
Publishing date	2024-03-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45628-x
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Article ; Online: Minimally invasive delivery of therapeutic agents by hydrogel injection into the pericardial cavity for cardiac repair.

Zhu, Dashuai / Li, Zhenhua / Huang, Ke / Caranasos, Thomas G / Rossi, Joseph S / Cheng, Ke

Nature communications

2021 Volume 12, Issue 1, Page(s) 1412

Abstract: Cardiac patches are an effective way to deliver therapeutics to the heart. However, such procedures are normally invasive and difficult to perform. Here, we develop and test a method to utilize the pericardial cavity as a natural "mold" for in situ ... ...

Abstract	Cardiac patches are an effective way to deliver therapeutics to the heart. However, such procedures are normally invasive and difficult to perform. Here, we develop and test a method to utilize the pericardial cavity as a natural "mold" for in situ cardiac patch formation after intrapericardial injection of therapeutics in biocompatible hydrogels. In rodent models of myocardial infarction, we demonstrate that intrapericardial injection is an effective and safe method to deliver hydrogels containing induced pluripotent stem cells-derived cardiac progenitor cells or mesenchymal stem cells-derived exosomes. After injection, the hydrogels form a cardiac patch-like structure in the pericardial cavity, mitigating immune response and increasing the cardiac retention of the therapeutics. With robust cardiovascular repair and stimulation of epicardium-derived cells, the delivered therapeutics mitigate cardiac remodeling and improve cardiac functions post myocardial infarction. Furthermore, we demonstrate the feasibility of minimally-invasive intrapericardial injection in a clinically-relevant porcine model. Collectively, our study establishes intrapericardial injection as a safe and effective method to deliver therapeutic-bearing hydrogels to the heart for cardiac repair.
MeSH term(s)	Animals ; Cardiac Surgical Procedures ; Cardiovascular Agents/administration & dosage ; Cell Differentiation/physiology ; Drug Delivery Systems/methods ; Exosomes/metabolism ; Extracellular Matrix/chemistry ; Hydrogels/administration & dosage ; Hydrogels/chemistry ; Induced Pluripotent Stem Cells/transplantation ; Male ; Materials Testing ; Mesenchymal Stem Cells/cytology ; Mice ; Minimally Invasive Surgical Procedures/methods ; Myocardial Infarction/drug therapy ; Myocardial Infarction/pathology ; Myocardial Infarction/therapy ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/physiology ; Pericardium ; Rats ; Swine
Chemical Substances	Cardiovascular Agents ; Hydrogels
Language	English
Publishing date	2021-03-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-21682-7
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