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  1. Article ; Online: Flexing Their Muscles: Maturation of Stem Cell-Derived Cardiomyocytes on Elastomeric Substrates to Enhance Cardiac Repair.

    Karbassi, Elaheh / Murry, Charles E

    Circulation

    2022  Volume 145, Issue 18, Page(s) 1427–1430

    MeSH term(s) Elasticity ; Humans ; Myocytes, Cardiac ; Stem Cells
    Language English
    Publishing date 2022-05-02
    Publishing country United States
    Document type Editorial ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.122.059079
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Cell Therapy Strategies With No Safety Concerns and Demonstrated Benefits Warrant Study - Reply.

    Nakamura, Kenta / Murry, Charles E

    Circulation journal : official journal of the Japanese Circulation Society

    2020  Volume 84, Issue 11, Page(s) 2122

    MeSH term(s) Cell- and Tissue-Based Therapy ; Heart
    Language English
    Publishing date 2020-10-10
    Publishing country Japan
    Document type Letter ; Comment
    ZDB-ID 2068090-9
    ISSN 1347-4820 ; 1346-9843
    ISSN (online) 1347-4820
    ISSN 1346-9843
    DOI 10.1253/circj.CJ-20-0928
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Lost in the fire.

    Marchianò, Silvia / Murry, Charles E

    Science (New York, N.Y.)

    2019  Volume 364, Issue 6436, Page(s) 123–124

    MeSH term(s) Conservation of Natural Resources ; Fires
    Language English
    Publishing date 2019-04-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.aax1006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Targeted CRISPR activation is functional in engineered human pluripotent stem cells but undergoes silencing after differentiation into cardiomyocytes and endothelium.

    Karbassi, Elaheh / Padgett, Ruby / Bertero, Alessandro / Reinecke, Hans / Klaiman, Jordan M / Yang, Xiulan / Hauschka, Stephen D / Murry, Charles E

    Cellular and molecular life sciences : CMLS

    2024  Volume 81, Issue 1, Page(s) 95

    Abstract: Human induced pluripotent stem cells (hiPSCs) offer opportunities to study human biology where primary cell types are limited. CRISPR technology allows forward genetic screens using engineered Cas9-expressing cells. Here, we sought to generate a CRISPR ... ...

    Abstract Human induced pluripotent stem cells (hiPSCs) offer opportunities to study human biology where primary cell types are limited. CRISPR technology allows forward genetic screens using engineered Cas9-expressing cells. Here, we sought to generate a CRISPR activation (CRISPRa) hiPSC line to activate endogenous genes during pluripotency and differentiation. We first targeted catalytically inactive Cas9 fused to VP64, p65 and Rta activators (dCas9-VPR) regulated by the constitutive CAG promoter to the AAVS1 safe harbor site. These CRISPRa hiPSC lines effectively activate target genes in pluripotency, however the dCas9-VPR transgene expression is silenced after differentiation into cardiomyocytes and endothelial cells. To understand this silencing, we systematically tested different safe harbor sites and different promoters. Targeting to safe harbor sites hROSA26 and CLYBL loci also yielded hiPSCs that expressed dCas9-VPR in pluripotency but silenced during differentiation. Muscle-specific regulatory cassettes, derived from cardiac troponin T or muscle creatine kinase promoters, were also silent after differentiation when dCas9-VPR was introduced. In contrast, in cell lines where the dCas9-VPR sequence was replaced with cDNAs encoding fluorescent proteins, expression persisted during differentiation in all loci and with all promoters. Promoter DNA was hypermethylated in CRISPRa-engineered lines, and demethylation with 5-azacytidine enhanced dCas9-VPR gene expression. In summary, the dCas9-VPR cDNA is readily expressed from multiple loci during pluripotency but induces silencing in a locus- and promoter-independent manner during differentiation to mesoderm derivatives. Researchers intending to use this CRISPRa strategy during stem cell differentiation should pilot their system to ensure it remains active in their population of interest.
    MeSH term(s) Humans ; Myocytes, Cardiac ; Endothelial Cells ; Induced Pluripotent Stem Cells ; Pluripotent Stem Cells ; Cell Differentiation/genetics ; Endothelium
    Language English
    Publishing date 2024-02-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-023-05101-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Quantifying Microvascular Structure in Healthy and Infarcted Rat Hearts Using Optical Coherence Tomography Angiography.

    Xie, Zhiying / Zeinstra, Nicole / Kirby, Mitchell A / Le, Nhan Minh / Murry, Charles E / Zheng, Ying / Wang, Ruikang K

    IEEE transactions on medical imaging

    2024  Volume PP

    Abstract: Myocardial infarction (MI) is a life-threatening medical emergency resulting in coronary microvascular dysregulation and heart muscle damage. One of the primary characteristics of MI is capillary loss, which plays a significant role in the progression of ...

    Abstract Myocardial infarction (MI) is a life-threatening medical emergency resulting in coronary microvascular dysregulation and heart muscle damage. One of the primary characteristics of MI is capillary loss, which plays a significant role in the progression of this cardiovascular condition. In this study, we utilized optical coherence tomography angiography (OCTA) to image coronary microcirculation in fixed rat hearts, aiming to analyze coronary microvascular impairment post-infarction. Various angiographic metrics are presented to quantify vascular features, including the vessel area density, vessel complexity index, vessel tortuosity index, and flow impairment. Pathological differences identified from OCTA analysis are corroborated with histological analysis. The quantitative assessments reveal a significant decrease in microvascular density in the capillary-sized vessels and an enlargement for the arteriole/venule-sized vessels. Further, microvascular tortuosity and complexity exhibit an increase after myocardial infarction. The results underscore the feasibility of using OCTA to offer qualitative microvascular details and quantitative metrics, providing insights into coronary vascular network remodeling during disease progression and response to therapy.
    Language English
    Publishing date 2024-04-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 622531-7
    ISSN 1558-254X ; 0278-0062
    ISSN (online) 1558-254X
    ISSN 0278-0062
    DOI 10.1109/TMI.2024.3381934
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Graft-host coupling changes can lead to engraftment arrhythmia: a computational study.

    Gibbs, Chelsea E / Marchianó, Silvia / Zhang, Kelly / Yang, Xiulan / Murry, Charles E / Boyle, Patrick M

    The Journal of physiology

    2023  Volume 601, Issue 13, Page(s) 2733–2749

    Abstract: After myocardial infarction (MI), a significant portion of heart muscle is replaced with scar tissue, progressively leading to heart failure. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CM) offer a promising option for improving cardiac ... ...

    Abstract After myocardial infarction (MI), a significant portion of heart muscle is replaced with scar tissue, progressively leading to heart failure. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CM) offer a promising option for improving cardiac function after MI. However, hPSC-CM transplantation can lead to engraftment arrhythmia (EA). EA is a transient phenomenon arising shortly after transplantation then spontaneously resolving after a few weeks. The underlying mechanism of EA is unknown. We hypothesize that EA may be explained partially by time-varying, spatially heterogeneous, graft-host electrical coupling. Here, we created computational slice models derived from histological images that reflect different configuration of grafts in the infarcted ventricle. We ran simulations with varying degrees of connection imposed upon the graft-host perimeter to assess how heterogeneous electrical coupling affected EA with non-conductive scar, slow-conducting scar and scar replaced by host myocardium. We also quantified the effect of variation in intrinsic graft conductivity. Susceptibility to EA initially increased and subsequently decreased with increasing graft-host coupling, suggesting the waxing and waning of EA is regulated by progressive increases in graft-host coupling. Different spatial distributions of graft, host and scar yielded markedly different susceptibility curves. Computationally replacing non-conductive scar with host myocardium or slow-conducting scar, and increasing intrinsic graft conductivity both demonstrated potential means to blunt EA vulnerability. These data show how graft location, especially relative to scar, along with its dynamic electrical coupling to host, can influence EA burden; moreover, they offer a rational base for further studies aimed to define the optimal delivery of hPSC-CM injection. KEY POINTS: Human pluripotent stem cell-derived cardiomyocytes (hPSC-CM) hold great cardiac regenerative potential but can also cause engraftment arrhythmias (EA). Spatiotemporal evolution in the pattern of electrical coupling between injected hPSC-CMs and surrounding host myocardium may explain the dynamics of EA observed in large animal models. We conducted simulations in histology-derived 2D slice computational models to assess the effects of heterogeneous graft-host electrical coupling on EA propensity, with or without scar tissue. Our findings suggest spatiotemporally heterogeneous graft-host coupling can create an electrophysiological milieu that favours graft-initiated host excitation, a surrogate metric of EA susceptibility. Removing scar from our models reduced but did not abolish the propensity for this phenomenon. Conversely, reduced intra-graft electrical connectedness increased the incidence of graft-initiated host excitation. The computational framework created for this study can be used to generate new hypotheses, targeted delivery of hPSC-CMs.
    MeSH term(s) Animals ; Humans ; Cicatrix/pathology ; Myocardium/pathology ; Myocytes, Cardiac/pathology ; Myocardial Infarction/pathology ; Arrhythmias, Cardiac ; Cell Differentiation
    Language English
    Publishing date 2023-04-25
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/JP284244
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Function Follows Form - A Review of Cardiac Cell Therapy.

    Nakamura, Kenta / Murry, Charles E

    Circulation journal : official journal of the Japanese Circulation Society

    2019  Volume 83, Issue 12, Page(s) 2399–2412

    Abstract: The investment of nearly 2 decades of clinical investigation into cardiac cell therapy has yet to change cardiovascular practice. Recent insights into the mechanism of cardiac regeneration help explain these results and provide important context in which ...

    Abstract The investment of nearly 2 decades of clinical investigation into cardiac cell therapy has yet to change cardiovascular practice. Recent insights into the mechanism of cardiac regeneration help explain these results and provide important context in which we can develop next-generation therapies. Non-contractile cells such as bone marrow or adult heart derivatives neither engraft long-term nor induce new muscle formation. Correspondingly, these cells offer little functional benefit to infarct patients. In contrast, preclinical data indicate that transplantation of bona fide cardiomyocytes derived from pluripotent stem cells induces direct remuscularization. This new myocardium beats synchronously with the host heart and induces substantial contractile benefits in macaque monkeys, suggesting that regeneration of contractile myocardium is required to fully recover function. Through a review of the preclinical and clinical trials of cardiac cell therapy, distinguishing the primary mechanism of benefit as either contractile or non-contractile helps appreciate the barriers to cardiac repair and establishes a rational path to optimizing therapeutic benefit.
    MeSH term(s) Animals ; Cell Differentiation ; Cell Proliferation ; Cell Survival ; Graft Survival ; Heart Diseases/pathology ; Heart Diseases/physiopathology ; Heart Diseases/surgery ; Humans ; Myocardial Contraction ; Myocardium/pathology ; Myocytes, Cardiac/transplantation ; Recovery of Function ; Regeneration ; Stem Cell Transplantation/adverse effects ; Treatment Outcome
    Language English
    Publishing date 2019-11-13
    Publishing country Japan
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2068090-9
    ISSN 1347-4820 ; 1346-9843
    ISSN (online) 1347-4820
    ISSN 1346-9843
    DOI 10.1253/circj.CJ-19-0567
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: High-resolution 3D fluorescent imaging of intact tissues.

    El-Nachef, Danny / Martinson, Amy M / Yang, Xiulan / Murry, Charles E / MacLellan, W Robb

    International journal of cardiology and cardiovascular diseases

    2022  Volume 1, Issue 1, Page(s) 1–14

    Abstract: Histological analysis of fluorescently labeled tissues has been a critical tool to understand molecular ... ...

    Abstract Histological analysis of fluorescently labeled tissues has been a critical tool to understand molecular organization
    Language English
    Publishing date 2022-02-19
    Publishing country United States
    Document type Journal Article
    ISSN 2768-5640
    ISSN (online) 2768-5640
    DOI 10.46439/cardiology.1.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Stem cells and the heart-the road ahead.

    Murry, Charles E / MacLellan, W Robb

    Science (New York, N.Y.)

    2020  Volume 367, Issue 6480, Page(s) 854–855

    MeSH term(s) Animals ; Cell- and Tissue-Based Therapy/methods ; Gene Editing ; Graft Rejection/genetics ; Graft Rejection/immunology ; Heart Diseases/therapy ; Humans ; Immunity/genetics ; Macaca ; Myocytes, Cardiac/immunology ; Myocytes, Cardiac/transplantation ; Pluripotent Stem Cells
    Language English
    Publishing date 2020-02-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.aaz3650
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Sustained miRNA release regenerates the heart.

    Mitzelfelt, Katie A / Murry, Charles E

    Nature biomedical engineering

    2018  Volume 1, Issue 12, Page(s) 931–933

    MeSH term(s) Animals ; Cell Proliferation/drug effects ; Drug Delivery Systems ; Hydrogels/administration & dosage ; Mice ; MicroRNAs/administration & dosage ; Myocytes, Cardiac/drug effects ; Myocytes, Cardiac/physiology ; Regeneration/drug effects
    Chemical Substances Hydrogels ; MicroRNAs
    Language English
    Publishing date 2018-01-01
    Publishing country England
    Document type News
    ISSN 2157-846X
    ISSN (online) 2157-846X
    DOI 10.1038/s41551-017-0171-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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