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  1. Article ; Online: Pre-transplant infusion of donor leukocytes treated with extracorporeal photochemotherapy induces immune hypo-responsiveness and long-term allograft survival in murine models

    Jennifer Schneiderman / Longhui Qiu / Xin Yi Yeap / Xin Kang / Feibo Zheng / Junsheng Ye / Yan Xie / Jiao-Jing Wang / Yuvaraj Sambandam / James Mathew / Lin Li / Joseph Leventhal / Richard L. Edelson / Zheng Jenny Zhang

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 16

    Abstract: Abstract Recipients of solid organ transplantation (SOT) rely on life-long immunosuppression (IS), which is associated with significant side effects. Extracorporeal photochemotherapy (ECP) is a safe, existing cellular therapy used to treat transplant ... ...

    Abstract Abstract Recipients of solid organ transplantation (SOT) rely on life-long immunosuppression (IS), which is associated with significant side effects. Extracorporeal photochemotherapy (ECP) is a safe, existing cellular therapy used to treat transplant rejection by modulating the recipient’s own blood cells. We sought to induce donor-specific hypo-responsiveness of SOT recipients by infusing ECP-treated donor leukocytes prior to transplant. To this end, we utilized major histocompatibility complex mismatched rodent models of allogeneic cardiac, liver, and kidney transplantation to test this novel strategy. Leukocytes isolated from donor-matched spleens for ECP treatment (ECP-DL) were infused into transplant recipients seven days prior to SOT. Pre-transplant infusion of ECP-DL without additional IS was associated with prolonged graft survival in all models. This innovative approach promoted the production of tolerogenic dendritic cells and regulatory T-cells with subsequent inhibition of T-cell priming and differentiation, along with a significant reduction of donor-specific T-cells in the spleen and grafts of treated animals. This new application of donor-type ECP-treated leukocytes provides insight into the mechanisms behind ECP-induced immunoregulation and holds significant promise in the prevention of graft rejection and reduction in need of global immune suppressive therapy in patients following SOT.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: MCMV Dissemination from Latently-Infected Allografts Following Transplantation into Pre-Tolerized Recipients

    Sahil Shah / Matthew DeBerge / Andre Iovane / Shixian Yan / Longhui Qiu / Jiao-Jing Wang / Yashpal S. Kanwar / Mary Hummel / Zheng J. Zhang / Michael M. Abecassis / Xunrong Luo / Edward B. Thorp

    Pathogens, Vol 9, Iss 607, p

    2020  Volume 607

    Abstract: Transplantation tolerance is achieved when recipients are unresponsive to donor alloantigen yet mobilize against third-party antigens, including virus. After transplantation, cytomegalovirus (CMV) reactivation in latently-infected transplants reduces ... ...

    Abstract Transplantation tolerance is achieved when recipients are unresponsive to donor alloantigen yet mobilize against third-party antigens, including virus. After transplantation, cytomegalovirus (CMV) reactivation in latently-infected transplants reduces allograft viability. To determine if pre-tolerized recipients are resistant to viral dissemination in this setting, we transfused chemically-fixed donor splenocytes (1-ethyl-3- (3′-dimethyl-aminopropyl)-carbo-diimide (ECDI)-treated splenocytes (ECDIsp)) to induce donor antigen tolerance without immunosuppression. In parallel, we implanted donor islet cells to validate operational tolerance. These pre-tolerized recipients were implanted with murine CMV (MCMV) latently-infected donor kidneys (a validated model of CMV latency) to monitor graft inflammation and viral dissemination. Our results indicate that tolerance to donor islets was sustained in recipients after implantation of donor kidneys. In addition, kidney allografts implanted after ECDIsp and islet implantation exhibited low levels of fibrosis and tubulitis. In contrast, kidney cellular and innate immune infiltrates trended higher in the CMV group and exhibited increased markers of CD8 + T cell activation. Tolerance induction was unable to prevent increases in MCMV-specific CD8 + T cells or dissemination of viral IE-1 DNA. Our data suggest that latently-infected allografts are inherently more susceptible to inflammation that is associated with viral dissemination in pre-tolerized recipients. Thus, CMV latently-infected allografts require enhanced strategies to protect allograft integrity and viral spread.
    Keywords transplant tolerance ; donor specific transfusion ; cytomegalovirus ; latency ; Medicine ; R
    Language English
    Publishing date 2020-07-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article: Vascular scaffolds with enhanced antioxidant activity inhibit graft calcification

    Jiang, Bin / Guillermo A. Ameer / Jason A. Wertheim / Jiao-Jing Wang / Rachel Suen / Zheng J. Zhang

    Biomaterials. 2017,

    2017  

    Abstract: There is a need for off-the-shelf, small-diameter vascular grafts that are safe and exhibit high long-term patency. Decellularized tissues can potentially be used as vascular grafts; however, thrombogenic and unpredictable remodeling properties such as ... ...

    Abstract There is a need for off-the-shelf, small-diameter vascular grafts that are safe and exhibit high long-term patency. Decellularized tissues can potentially be used as vascular grafts; however, thrombogenic and unpredictable remodeling properties such as intimal hyperplasia and calcification are concerns that hinder their clinical use. The objective of this study was to investigate the long-term function and remodeling of extracellular matrix (ECM)-based vascular grafts composited with antioxidant poly(1, 8-octamethylene-citrate-co-cysteine) (POCC) with or without immobilized heparin. Rat aortas were decellularized to create the following vascular grafts: 1) ECM hybridized with POCC (Poly-ECM), 2) Poly-ECM subsequently functionalized with heparin (Poly-ECM-Hep), and 3) non-modified vascular ECM. Grafts were evaluated as interposition grafts in the abdominal aorta of adult rats at three months. All grafts displayed antioxidant activity, were patent, and exhibited minimal intramural cell infiltration with varying degrees of calcification. Areas of calcification co-localized with osteochondrogenic differentiation of vascular smooth muscle cells, lipid peroxidation, oxidized DNA damage, and cell apoptosis, suggesting an important role for oxidative stress in the calcification of grafts. The extent of calcification within grafts was inversely proportional to their antioxidant activity: Poly-ECM-Hep > ECM > Poly-ECM. The incorporation of antioxidants into vascular grafts may be a viable strategy to inhibit degenerative changes.
    Keywords adults ; antioxidant activity ; antioxidants ; aorta ; apoptosis ; calcification ; DNA damage ; extracellular matrix ; heparin ; hyperplasia ; lipid peroxidation ; myocytes ; oxidative stress ; rats ; smooth muscle
    Language English
    Size p. .
    Publishing place Elsevier Ltd
    Document type Article
    Note Pre-press version
    ZDB-ID 603079-8
    ISSN 0142-9612
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2017.08.014
    Database NAL-Catalogue (AGRICOLA)

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  4. Article: Nitric Oxide-Delivering High-Density Lipoprotein-like Nanoparticles as a Biomimetic Nanotherapy for Vascular Diseases

    Rink, Jonathan S / Wangqiang Sun / Sol Misener / Jiao-Jing Wang / Zheng Jenny Zhang / Melina R. Kibbe / Vinayak P. Dravid / Subbu Venkatraman / C. Shad Thaxton

    ACS applied materials & interfaces. 2018 Feb. 28, v. 10, no. 8

    2018  

    Abstract: Disorders of blood vessels cause a range of severe health problems. As a powerful vasodilator and cellular second messenger, nitric oxide (NO) is known to have beneficial vascular functions. However, NO typically has a short half-life and is not ... ...

    Abstract Disorders of blood vessels cause a range of severe health problems. As a powerful vasodilator and cellular second messenger, nitric oxide (NO) is known to have beneficial vascular functions. However, NO typically has a short half-life and is not specifically targeted. On the other hand, high-density lipoproteins (HDLs) are targeted natural nanoparticles (NPs) that transport cholesterol in the systemic circulation and whose protective effects in vascular homeostasis overlap with those of NO. Evolving the AuNP-templated HDL-like nanoparticles (HDL NPs), a platform of bioinspired HDL, we set up a targeted biomimetic nanotherapy for vascular disease that combines the functions of NO and HDL. A synthetic S-nitrosylated (SNO) phospholipid (1,2-dipalmitoyl-sn-glycero-3-phosphonitrosothioethanol) was synthesized and assembled with S-containing phospholipids and the principal protein of HDL, apolipoprotein A-I, to construct NO-delivering HDL-like particles (SNO HDL NPs). SNO HDL NPs self-assemble under mild conditions similar to natural processes, avoiding the complex postassembly modification needed for most synthetic NO-release nanoparticles. In vitro data demonstrate that the SNO HDL NPs merge the functional properties of NO and HDL into a targeted nanocarrier. Also, SNO HDL NPs were demonstrated to reduce ischemia/reperfusion injury in vivo in a mouse kidney transplant model and atherosclerotic plaque burden in a mouse model of atherosclerosis. Thus, the synthesis of SNO HDL NPs provides not only a bioinspired nanotherapy for vascular disease but also a foundation to construct diversified multifunctional platforms based on HDL NPs in the future.
    Keywords animal models ; apolipoprotein A-I ; atherosclerosis ; biomimetics ; blood vessels ; cholesterol ; functional properties ; half life ; high density lipoprotein ; homeostasis ; ischemia ; kidney transplant ; mice ; nanocarriers ; nanoparticles ; nitric oxide ; phospholipids ; protective effect
    Language English
    Dates of publication 2018-0228
    Size p. 6904-6916.
    Publishing place American Chemical Society
    Document type Article
    ISSN 1944-8252
    DOI 10.1021/acsami.7b18525
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: CD103 deficiency prevents graft-versus-host disease but spares graft-versus-tumor effects mediated by alloreactive CD8 T cells.

    Kechang Liu / Bryan A Anthony / Martha M Yearsly / Mehdi Hamadani / Alice Gaughan / Jiao-Jing Wang / Steven M Devine / Gregg A Hadley

    PLoS ONE, Vol 6, Iss 7, p e

    2011  Volume 21968

    Abstract: Graft-versus-host disease (GVHD) remains the main barrier to broader application of allogeneic hematopoietic stem cell transplantation (alloSCT) as a curative therapy for host malignancy. GVHD is mediated by allogeneic T cells directed against ... ...

    Abstract Graft-versus-host disease (GVHD) remains the main barrier to broader application of allogeneic hematopoietic stem cell transplantation (alloSCT) as a curative therapy for host malignancy. GVHD is mediated by allogeneic T cells directed against histocompatibility antigens expressed by host tissues. Based on previous studies, we postulated that the integrin CD103 is required for CD8-mediated GVHD, but not for graft-versus-tumor effects (GVT).We herein provide evidence in support of this hypothesis. To circumvent the potentially confounding influence of donor CD4 T cells, we developed an alloSCT model in which GVHD mortality is mediated by purified CD8 T cells. In this model, host-reactive CD8 T cells receive CD4 T cell help at the time of initial activation but not in the effector phase in which mature CD8 T effectors migrate into host tissues. We show that donor CD8 T cells from wild-type BALB/c mice primed to host alloantigens induce GVHD pathology and eliminate tumors of host origin in the absence of host CD4 T cells. Importantly, CD103 deficiency dramatically attenuated GVHD mortality, but had no detectable impact on the capacity to eliminate a tumor line of host origin. We provide evidence that CD103 is required for accumulation of donor CD8 T cells in the host intestinal epithelium but not in the tumor or host lymphoid compartments. Consistent with these data, CD103 was preferentially expressed by CD8 T cells infiltrating the host intestinal epithelium but not by those infiltrating the tumor, lamina propria, or lymphoid compartments. We further demonstrate that CD103 expression is not required for classic CD8 effector activities including cytokine production and cytotoxicity.These data indicate that CD103 deficiency inhibits GVHD pathology while sparing anti-tumor effects mediated by CD8 T cells, identifying CD103 blockade as an improved strategy for GVHD prophylaxis.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2011-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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