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  1. Article ; Online: Acellular Human Amniotic Fluid-Derived Extracellular Vesicles as Novel Anti-Inflammatory Therapeutics against SARS-CoV-2 Infection.

    Chanda, Debarati / Del Rivero, Tania / Ghimire, Roshan / More, Sunil / Mitrani, Maria Ines / Bellio, Michael A / Channappanavar, Rudragouda

    Viruses

    2024  Volume 16, Issue 2

    Abstract: The ongoing COVID-19 pandemic caused by SARS-CoV-2 is associated with acute respiratory distress syndrome (ARDS) and fatal pneumonia. Excessive inflammation caused by SARS-CoV-2 is the key driver of ARDS and lethal disease. Several FDA-approved drugs ... ...

    Abstract The ongoing COVID-19 pandemic caused by SARS-CoV-2 is associated with acute respiratory distress syndrome (ARDS) and fatal pneumonia. Excessive inflammation caused by SARS-CoV-2 is the key driver of ARDS and lethal disease. Several FDA-approved drugs that suppress virus replication are in clinical use. However, despite strong evidence for the role of virus-induced inflammation in severe COVID-19, no effective anti-inflammatory drug is available to control fatal inflammation as well as efficiently clear the virus. Therefore, there is an urgent need to identify biologically derived immunomodulators that suppress inflammation and promote antiviral immunity. In this study, we evaluated acellular human amniotic fluid (acAF) containing extracellular vesicles (hAF-EVs) as a potential non-toxic and safe biologic for immunomodulation during COVID-19. Our in vitro results showed that acAF significantly reduced inflammatory cytokine production in TLR2/4/7 and SARS-CoV-2 structural protein-stimulated mouse macrophages. Importantly, an intraperitoneal administration of acAF reduced morbidity and mortality in SARS-CoV-2-infected mice. A detailed examination of SARS-CoV-2-infected lungs revealed that the increased protection in acAF-treated mice was associated with reduced viral titers and levels of inflammatory myeloid cell infiltration. Collectively, our results identify a novel biologic that has potential to suppress excessive inflammation and enhance survival following SARS-CoV-2 infection, highlighting the translational potential of acAF against COVID-19.
    MeSH term(s) Humans ; Animals ; Mice ; COVID-19 ; SARS-CoV-2 ; Amniotic Fluid ; Pandemics ; Inflammation ; Respiratory Distress Syndrome ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Extracellular Vesicles ; Biological Products
    Chemical Substances Anti-Inflammatory Agents ; Biological Products
    Language English
    Publishing date 2024-02-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v16020273
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Extracellular vesicles: A promising therapy against SARS-CoV-2 infection.

    Leyfman, Yan / Gohring, Greta / Joshi, Muskan / Menon, Gayathri Pramil / Van de Kieft, Alexandra / Rivero, Tania Del / Bellio, Michael A / Mitrani, Maria Ines

    Molecular therapy : the journal of the American Society of Gene Therapy

    2023  Volume 31, Issue 5, Page(s) 1196–1200

    MeSH term(s) Humans ; COVID-19 ; SARS-CoV-2 ; Extracellular Vesicles
    Language English
    Publishing date 2023-05-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1016/j.ymthe.2023.03.033
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5640: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Human amniotic fluid derived extracellular vesicles attenuate T cell immune response.

    Del Rivero, Tania / Milberg, Julian / Bennett, Cassie / Mitrani, Maria Ines / Bellio, Michael A

    Frontiers in immunology

    2022  Volume 13, Page(s) 977809

    Abstract: Introduction: Extracellular vesicles isolated from human amniotic fluid (AF-EVs) have previously been found to modulate inflammation and macrophage infiltration in a mouse model. However, the effects of acellular amniotic fluid (acAF) or AF-EVs on the T- ...

    Abstract Introduction: Extracellular vesicles isolated from human amniotic fluid (AF-EVs) have previously been found to modulate inflammation and macrophage infiltration in a mouse model. However, the effects of acellular amniotic fluid (acAF) or AF-EVs on the T-Cell immune response have not been explored.
    Methods: In this study, we investigated the effects of acAF and AF-EVs on the T cell immune response in an in vitro cell culture model. Peripheral Blood Mononuclear Cells (PBMCs) were stimulated with Phytohemagglutinin (PHA) to induce the immune response and were subsequently treated with either serum-free media (vehicle), acAF, or concentrated AF-EVs.
    Results: Both acAF and AF-EV treatment suppressed PHA-induced T cell proliferation and PHA-induced T cell activation; however, treatment with concentrated AF-EVs had a greater effect. Additionally, both acAF and AF-EVs reduced PBMC pro-inflammatory cytokine release. AF-EVs were found to be taken up by both CD4+ and CD8+ effector T cell subsets.
    Conclusion: Overall, this data demonstrates that AF-EVs have a robust immunomodulatory effect on T cells and suggests AF-EVs could be used as an immunotherapeutic tool.
    MeSH term(s) Animals ; Mice ; Humans ; Amniotic Fluid ; Leukocytes, Mononuclear ; Extracellular Vesicles ; Cytokines ; Immunity
    Chemical Substances Cytokines
    Language English
    Publishing date 2022-11-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.977809
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Case Report: Administration of Amniotic Fluid-Derived Nanoparticles in Three Severely Ill COVID-19 Patients.

    Mitrani, Maria Ines / Bellio, Michael A / Sagel, Anthony / Saylor, Marie / Kapp, William / VanOsdol, Kathryn / Haskell, Gwendolyn / Stewart, Danique / Abdullah, Zanub / Santos, Ivan / Milberg, Julian / Arango, Alissa / Mitrani, Albert / Shapiro, George C

    Frontiers in medicine

    2021  Volume 8, Page(s) 583842

    Abstract: Rationale/Objectives: ...

    Abstract Rationale/Objectives:
    Language English
    Publishing date 2021-03-17
    Publishing country Switzerland
    Document type Case Reports
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2021.583842
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  5. Article ; Online: Proof-of-concept trial of an amniotic fluid-derived extracellular vesicle biologic for treating high risk patients with mild-to-moderate acute COVID-19 infection.

    Bellio, Michael A / Bennett, Cassie / Arango, Alissa / Khan, Aisha / Xu, Xiumin / Barrera, Cesar / Friedewald, Vincent / Mitrani, Maria Ines

    Biomaterials and biosystems

    2021  Volume 4, Page(s) 100031

    Abstract: A pandemic brought on by COVID-19 has created a scalable health crisis. The search to help alleviate COVID-19-related complications through therapeutics has become a necessity. Zofin is an investigational, acellular biologic derived from full-term ... ...

    Abstract A pandemic brought on by COVID-19 has created a scalable health crisis. The search to help alleviate COVID-19-related complications through therapeutics has become a necessity. Zofin is an investigational, acellular biologic derived from full-term perinatal amniotic fluid that contains extracellular vesicles. Extracellular nanoparticles as such have been studied for their immunomodulatory benefits via cellular therapeutics and, if applied to COVID-19-related inflammation, could benefit patient outcome. Subjects (
    Language English
    Publishing date 2021-11-24
    Publishing country England
    Document type Journal Article
    ISSN 2666-5344
    ISSN (online) 2666-5344
    DOI 10.1016/j.bbiosy.2021.100031
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Treatment of a COVID-19 long hauler with an amniotic fluid-derived extracellular vesicle biologic.

    Mitrani, Maria Ines / Bellio, Michael A / Meglin, Allen / Khan, Aisha / Xu, Xiumin / Haskell, Gwendolyn / Arango, Alissa / Shapiro, George C

    Respiratory medicine case reports

    2021  Volume 34, Page(s) 101502

    Abstract: Post-COVID-19 infection symptoms such as mental fog, tachycardia, and extreme fatigue are just a few of the symptoms wreaking havoc on patients' lives. Patients with long-term symptoms following COVID-19 are being called long haulers. To date, long ... ...

    Abstract Post-COVID-19 infection symptoms such as mental fog, tachycardia, and extreme fatigue are just a few of the symptoms wreaking havoc on patients' lives. Patients with long-term symptoms following COVID-19 are being called long haulers. To date, long haulers are receiving little to no guidance from physicians on their lingering COVID-19 symptoms with limited treatment options available. Zofin is an acellular biologic that contains the extracellular vesicle (EV) fraction of human amniotic fluid and is under investigation for use as a COVID-19 therapeutic. We obtained FDA and IRB approval to investigate the therapeutic use of Zofin in a single long hauler patient case experiencing prolonged shortness of breath and respiratory impairment. Administration of the EV product was shown to be safe. Furthermore, demonstrated respiratory improvements through chest X ray images and oxygen saturation measurement. The single patient IND studies were completed without any reported adverse events or safety concerns. Furthermore, these completed studies demonstrate the feasibility and a therapeutic potential of amniotic fluid-derived EVs for COVID-19 long hauler intervention.
    Language English
    Publishing date 2021-08-30
    Publishing country England
    Document type Case Reports
    ZDB-ID 2666110-X
    ISSN 2213-0071
    ISSN 2213-0071
    DOI 10.1016/j.rmcr.2021.101502
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Case Report

    Maria Ines Mitrani / Michael A. Bellio / Anthony Sagel / Marie Saylor / William Kapp / Kathryn VanOsdol / Gwendolyn Haskell / Danique Stewart / Zanub Abdullah / Ivan Santos / Julian Milberg / Alissa Arango / Albert Mitrani / George C. Shapiro

    Frontiers in Medicine, Vol

    Administration of Amniotic Fluid-Derived Nanoparticles in Three Severely Ill COVID-19 Patients

    2021  Volume 8

    Abstract: Rationale/Objectives: A human coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak worldwide. There is an urgent need to develop new interventions to suppress the excessive immune response, protect alveolar function, and ... ...

    Abstract Rationale/Objectives: A human coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak worldwide. There is an urgent need to develop new interventions to suppress the excessive immune response, protect alveolar function, and repair lung and systemic organ damage. Zofin (previously known as Organicell Flow) is a novel therapeutic that is derived from the soluble and nanoparticle fraction (extracellular vesicles and exosomes) of human amniotic fluid. Here within, we present the clinical outcomes after Zofin treatment in three critically ill patients suffering from severe, multi-organ complications induced by COVID-19 infection. All patients were diagnosed with COVID-19, developed respiratory failure, and were hospitalized for more than 40 days.Methods: Zofin was administered to patients concurrently with ongoing medical care who were monitored for 28-days post-therapy. SOFA score assessment, chest X-rays, and inflammatory biomarker testing was performed.Main Results: There were no adverse events associated with the therapy. The patients showed improvements in ICU clinical status and experienced respiratory improvements. Acute delirium experienced by patients completely resolved and inflammatory biomarkers improved.Conclusions: Primary outcomes demonstrate the therapy was safe, accessible, and feasible. This is the first demonstration of human amniotic fluid-derived nanoparticles as a safe and potentially efficacious therapeutic treatment for respiratory failure induced by COVID-19 infection.
    Keywords COVID-19 ; critical care ; ARDS (acute respiratory distress syndrome) ; exosomes ; amniotic fluid (AF) ; extracellular vesicles ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Amniotic fluid-derived extracellular vesicles: characterization and therapeutic efficacy in an experimental model of bronchopulmonary dysplasia.

    Bellio, Michael A / Young, Karen C / Milberg, Julian / Santos, Ivan / Abdullah, Zanub / Stewart, Danique / Arango, Alissa / Chen, Pingping / Huang, Jian / Williams, Kevin / Kelly, Kaitlyn / Sterling, Shanique / Khan, Aisha / Xu, Xiumin / Shapiro, George C / Mitrani, Maria Ines

    Cytotherapy

    2021  Volume 23, Issue 12, Page(s) 1097–1107

    Abstract: Background aims: Extracellular vesicles (EVs) are being tested for their use as novel therapeutics. However, the optimal source of EVs is currently under investigation. Amniotic fluid (AF) is a natural source of EVs that can be easily obtained for use ... ...

    Abstract Background aims: Extracellular vesicles (EVs) are being tested for their use as novel therapeutics. However, the optimal source of EVs is currently under investigation. Amniotic fluid (AF) is a natural source of EVs that can be easily obtained for use in regenerative medicine, yet AF-EV characterization has not been fully explored.
    Methods: Here the authors demonstrate AF as a rich source of EVs and identify the microRNA and proteomic cargo. Bioinformatics analysis of this cargo revealed multiple pathway targets, including immunomodulatory, anti-inflammatory and free radical scavenging networks. The authors further demonstrated the therapeutic potential of this EV product as a novel preventative agent for bronchopulmonary dysplasia (BPD).
    Results: Intra-tracheal administration of AF-EVs preserved alveolar development, attenuated vascular remodeling and pulmonary hypertension, decreased lung pro-inflammatory cytokine expression and reduced macrophage infiltration in an experimental BPD model.
    Conclusions: The authors' results suggest that AF is a viable biological fluid for EV harvest and that AF-EVs have strong therapeutic potential for pulmonary diseases, such as BPD, warranting further development to transition this novel EV product into the clinic.
    MeSH term(s) Amniotic Fluid ; Animals ; Bronchopulmonary Dysplasia/therapy ; Disease Models, Animal ; Extracellular Vesicles ; Humans ; Infant, Newborn ; Models, Theoretical ; Proteomics ; Rats, Sprague-Dawley ; Rats
    Language English
    Publishing date 2021-09-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2039821-9
    ISSN 1477-2566 ; 1465-3249
    ISSN (online) 1477-2566
    ISSN 1465-3249
    DOI 10.1016/j.jcyt.2021.07.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5601: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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