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  1. Article ; Online: Stacking thick perfusable human microvascular grafts enables dense vascularity and rapid integration into infarcted rat hearts

    Zeinstra, Nicole / Frey, Ariana L. / Xie, Zhiying / Blakely, Leslie P. / Wang, Ruikang K. / Murry, Charles E. / Zheng, Ying

    Biomaterials. 2023 July 18, p.122250-

    2023  , Page(s) 122250–

    Abstract: Fabrication of large-scale engineered tissues requires extensive vascularization to support tissue survival and function. Here, we report a modular fabrication approach, by stacking of patterned collagen membranes, to generate thick (2 mm and beyond), ... ...

    Abstract Fabrication of large-scale engineered tissues requires extensive vascularization to support tissue survival and function. Here, we report a modular fabrication approach, by stacking of patterned collagen membranes, to generate thick (2 mm and beyond), large, three-dimensional, perfusable networks of endothelialized vasculature. In vitro, these perfusable vascular networks exhibit remodeling and evenly distributed perfusion among layers, while maintaining their patterned, open-lumen architecture. Compared to non-perfusable, self-assembled vasculature, constructs with perfusable vasculature demonstrated increased gene expression indicative of vascular development and angiogenesis. Upon implantation onto infarcted rat hearts, perfusable vascular networks attain greater host vascular integration than self-assembled controls, indicated by 2.5-fold greater perfused vascular density measured by histological analysis and 5-fold greater perfusion rate measured by optical microangiography. Together, the success of fabricating thick, perfusable tissues with dense vascularity and rapid anastomoses represents an important step forward for vascular bioengineering, and paves the way towards more complex, large scale, highly metabolic engineered tissues.
    Keywords angiogenesis ; biocompatible materials ; collagen ; gene expression ; histology ; humans ; rats ; Cardiac tissue engineering ; Microvasculature ; Perfusable ; Modular fabrication ; Host integration
    Language English
    Dates of publication 2023-0718
    Publishing place Elsevier Ltd
    Document type Article ; Online
    Note Pre-press version
    ZDB-ID 603079-8
    ISSN 0142-9612
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2023.122250
    Database NAL-Catalogue (AGRICOLA)

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  2. Article ; Online: Stacking thick perfusable human microvascular grafts enables dense vascularity and rapid integration into infarcted rat hearts.

    Zeinstra, Nicole / Frey, Ariana L / Xie, Zhiying / Blakely, Leslie P / Wang, Ruikang K / Murry, Charles E / Zheng, Ying

    Biomaterials

    2023  Volume 301, Page(s) 122250

    Abstract: Fabrication of large-scale engineered tissues requires extensive vascularization to support tissue survival and function. Here, we report a modular fabrication approach, by stacking of patterned collagen membranes, to generate thick (2 mm and beyond), ... ...

    Abstract Fabrication of large-scale engineered tissues requires extensive vascularization to support tissue survival and function. Here, we report a modular fabrication approach, by stacking of patterned collagen membranes, to generate thick (2 mm and beyond), large, three-dimensional, perfusable networks of endothelialized vasculature. In vitro, these perfusable vascular networks exhibit remodeling and evenly distributed perfusion among layers, while maintaining their patterned, open-lumen architecture. Compared to non-perfusable, self-assembled vasculature, constructs with perfusable vasculature demonstrated increased gene expression indicative of vascular development and angiogenesis. Upon implantation onto infarcted rat hearts, perfusable vascular networks attain greater host vascular integration than self-assembled controls, indicated by 2.5-fold greater perfused vascular density measured by histological analysis and 5-fold greater perfusion rate measured by optical microangiography. Together, the success of fabricating thick, perfusable tissues with dense vascularity and rapid anastomoses represents an important step forward for vascular bioengineering, and paves the way towards more complex, large scale, highly metabolic engineered tissues.
    MeSH term(s) Rats ; Animals ; Humans ; Tissue Engineering/methods ; Neovascularization, Pathologic ; Collagen ; Tissue Scaffolds
    Chemical Substances Collagen (9007-34-5)
    Language English
    Publishing date 2023-07-18
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 603079-8
    ISSN 1878-5905 ; 0142-9612
    ISSN (online) 1878-5905
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2023.122250
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Symposium review: Targeting antimicrobial defenses of the udder through an intrinsic cellular pathway.

    Nelson, Corwin D / Merriman, Kathryn E / Poindexter, Michael B / Kweh, Mercedes F / Blakely, Leslie P

    Journal of dairy science

    2018  Volume 101, Issue 3, Page(s) 2753–2761

    Abstract: The bovine innate immune system has a strong repertoire of antimicrobial defenses to rapidly attack infectious pathogens that evade physical barriers of the udder. Exploration of the intracrine vitamin D pathway of bovine macrophages has improved ... ...

    Abstract The bovine innate immune system has a strong repertoire of antimicrobial defenses to rapidly attack infectious pathogens that evade physical barriers of the udder. Exploration of the intracrine vitamin D pathway of bovine macrophages has improved understanding of the signals that initiate antimicrobial defenses that protect the udder. In the intracrine vitamin D pathway, pathogen recognition receptors upregulate CYP27B1 mRNA that encodes for the enzyme that converts 25-hydroxyvitamin D [25(OH)D
    MeSH term(s) Animals ; Cattle ; Female ; Lactation ; Macrophages/metabolism ; Mammary Glands, Animal/immunology ; Mammary Glands, Animal/microbiology ; Mastitis, Bovine/immunology ; Mastitis, Bovine/metabolism ; Mastitis, Bovine/microbiology ; Metabolic Networks and Pathways ; Streptococcal Infections/immunology ; Streptococcal Infections/veterinary ; Vitamin D/metabolism ; Vitamins/metabolism
    Chemical Substances Vitamins ; Vitamin D (1406-16-2)
    Language English
    Publishing date 2018-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 242499-x
    ISSN 1525-3198 ; 0022-0302
    ISSN (online) 1525-3198
    ISSN 0022-0302
    DOI 10.3168/jds.2017-13426
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Gene editing to prevent ventricular arrhythmias associated with cardiomyocyte cell therapy.

    Marchiano, Silvia / Nakamura, Kenta / Reinecke, Hans / Neidig, Lauren / Lai, Michael / Kadota, Shin / Perbellini, Filippo / Yang, Xiulan / Klaiman, Jordan M / Blakely, Leslie P / Karbassi, Elaheh / Fields, Paul A / Fenix, Aidan M / Beussman, Kevin M / Jayabalu, Anu / Kalucki, Faith A / Potter, Jennifer C / Futakuchi-Tsuchida, Akiko / Weber, Gerhard J /
    Dupras, Sarah / Tsuchida, Hiroshi / Pabon, Lil / Wang, Lili / Knollmann, Björn C / Kattman, Steven / Thies, R Scott / Sniadecki, Nathan / MacLellan, W Robb / Bertero, Alessandro / Murry, Charles E

    Cell stem cell

    2023  Volume 30, Issue 5, Page(s) 741

    Language English
    Publishing date 2023-04-25
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2375354-7
    ISSN 1875-9777 ; 1934-5909
    ISSN (online) 1875-9777
    ISSN 1934-5909
    DOI 10.1016/j.stem.2023.04.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Gene editing to prevent ventricular arrhythmias associated with cardiomyocyte cell therapy.

    Marchiano, Silvia / Nakamura, Kenta / Reinecke, Hans / Neidig, Lauren / Lai, Michael / Kadota, Shin / Perbellini, Filippo / Yang, Xiulan / Klaiman, Jordan M / Blakely, Leslie P / Karbassi, Elaheh / Fields, Paul A / Fenix, Aidan M / Beussman, Kevin M / Jayabalu, Anu / Kalucki, Faith A / Potter, Jennifer C / Futakuchi-Tsuchida, Akiko / Weber, Gerhard J /
    Dupras, Sarah / Tsuchida, Hiroshi / Pabon, Lil / Wang, Lili / Knollmann, Björn C / Kattman, Steven / Thies, R Scott / Sniadecki, Nathan / MacLellan, W Robb / Bertero, Alessandro / Murry, Charles E

    Cell stem cell

    2023  Volume 30, Issue 4, Page(s) 396–414.e9

    Abstract: Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) offer a promising cell-based therapy for myocardial infarction. However, the presence of transitory ventricular arrhythmias, termed engraftment arrhythmias (EAs), hampers clinical applications. ...

    Abstract Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) offer a promising cell-based therapy for myocardial infarction. However, the presence of transitory ventricular arrhythmias, termed engraftment arrhythmias (EAs), hampers clinical applications. We hypothesized that EA results from pacemaker-like activity of hPSC-CMs associated with their developmental immaturity. We characterized ion channel expression patterns during maturation of transplanted hPSC-CMs and used pharmacology and genome editing to identify those responsible for automaticity in vitro. Multiple engineered cell lines were then transplanted in vivo into uninjured porcine hearts. Abolishing depolarization-associated genes HCN4, CACNA1H, and SLC8A1, along with overexpressing hyperpolarization-associated KCNJ2, creates hPSC-CMs that lack automaticity but contract when externally stimulated. When transplanted in vivo, these cells engrafted and coupled electromechanically with host cardiomyocytes without causing sustained EAs. This study supports the hypothesis that the immature electrophysiological prolife of hPSC-CMs mechanistically underlies EA. Thus, targeting automaticity should improve the safety profile of hPSC-CMs for cardiac remuscularization.
    MeSH term(s) Humans ; Animals ; Swine ; Myocytes, Cardiac/metabolism ; Gene Editing ; Cell Line ; Arrhythmias, Cardiac/genetics ; Arrhythmias, Cardiac/therapy ; Arrhythmias, Cardiac/metabolism ; Cell- and Tissue-Based Therapy ; Cell Differentiation/genetics
    Language English
    Publishing date 2023-04-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2375354-7
    ISSN 1875-9777 ; 1934-5909
    ISSN (online) 1875-9777
    ISSN 1934-5909
    DOI 10.1016/j.stem.2023.03.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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