LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 9 of total 9

Search options

  1. Book ; Online ; Thesis: Next Generation Mesenchymal Stromal Cells for Regenerative Purposes - Manipulation of the Cellular Phenotype Using Biomaterials and Non-viral Gene Transfer

    Drzeniek, Norman Michael [Verfasser]

    2024  

    Author's details Norman Michael Drzeniek
    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Language English
    Publisher Medizinische Fakultät Charité - Universitätsmedizin Berlin
    Publishing place Berlin
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

    More links

    Kategorien

  2. Article: Implantable Biomaterials for Peripheral Nerve Regeneration-Technology Trends and Translational Tribulations.

    Sanchez Rezza, Angela / Kulahci, Yalcin / Gorantla, Vijay S / Zor, Fatih / Drzeniek, Norman M

    Frontiers in bioengineering and biotechnology

    2022  Volume 10, Page(s) 863969

    Abstract: The use of autografted nerve in surgical repair of peripheral nerve injuries (PNI) is severely limited due to donor site morbidity and restricted tissue availability. As an alternative, synthetic nerve guidance channels (NGCs) are available on the market ...

    Abstract The use of autografted nerve in surgical repair of peripheral nerve injuries (PNI) is severely limited due to donor site morbidity and restricted tissue availability. As an alternative, synthetic nerve guidance channels (NGCs) are available on the market for surgical nerve repair, but they fail to promote nerve regeneration across larger critical gap nerve injuries. Therefore, such injuries remain unaddressed, result in poor healing outcomes and are a limiting factor in limb reconstruction and transplantation. On the other hand, a myriad of advanced biomaterial strategies to address critical nerve injuries are proposed in preclinical literature but only few of those have found their way into clinical practice. The design of synthetic nerve grafts should follow rational criteria and make use of a combination of bioinstructive cues to actively promote nerve regeneration. To identify the most promising NGC designs for translation into applicable products, thorough mode of action studies, standardized readouts and validation in large animals are needed. We identify design criteria for NGC fabrication according to the current state of research, give a broad overview of bioactive and functionalized biomaterials and highlight emerging composite implant strategies using therapeutic cells, soluble factors, structural features and intrinsically conductive substrates. Finally, we discuss translational progress in bioartificial conduits for nerve repair from the surgeon's perspective and give an outlook toward future challenges in the field.
    Language English
    Publishing date 2022-04-27
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2719493-0
    ISSN 2296-4185
    ISSN 2296-4185
    DOI 10.3389/fbioe.2022.863969
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: In Vitro Transcribed mRNA Immunogenicity Induces Chemokine-Mediated Lymphocyte Recruitment and Can Be Gradually Tailored by Uridine Modification.

    Drzeniek, Norman M / Kahwaji, Nourhan / Picht, Samira / Dimitriou, Ioanna Maria / Schlickeiser, Stephan / Moradian, Hanieh / Geissler, Sven / Schmueck-Henneresse, Michael / Gossen, Manfred / Volk, Hans-Dieter

    Advanced science (Weinheim, Baden-Wurttemberg, Germany)

    2024  , Page(s) e2308447

    Abstract: Beyond SARS-CoV2 vaccines, mRNA drugs are being explored to overcome today's greatest healthcare burdens, including cancer and cardiovascular disease. Synthetic mRNA triggers immune responses in transfected cells, which can be reduced by chemically ... ...

    Abstract Beyond SARS-CoV2 vaccines, mRNA drugs are being explored to overcome today's greatest healthcare burdens, including cancer and cardiovascular disease. Synthetic mRNA triggers immune responses in transfected cells, which can be reduced by chemically modified nucleotides. However, the side effects of mRNA-triggered immune activation on cell function and how different nucleotides, such as the N1-methylpseudouridine (m1Ψ) used in SARS-CoV2 vaccines, can modulate cellular responses is not fully understood. Here, cellular responses toward a library of uridine-modified mRNAs are investigated in primary human cells. Targeted proteomics analyses reveal that unmodified mRNA induces a pro-inflammatory paracrine pattern marked by the secretion of chemokines, which recruit T and B lymphocytes toward transfected cells. Importantly, the magnitude of mRNA-induced changes in cell function varies quantitatively between unmodified, Ψ-, m1Ψ-, and 5moU-modified mRNA and can be gradually tailored, with implications for deliberately exploiting this effect in mRNA drug design. Indeed, both the immunosuppressive effect of stromal cells on T-cell proliferation, and the anti-inflammatory effect of IL-10 mRNA are enhanced by appropriate uridine modification. The results provide new insights into the effects of mRNA drugs on cell function and cell-cell communication and open new possibilities to tailor mRNA-triggered immune activation to the desired pro- or anti-inflammatory application.
    Language English
    Publishing date 2024-03-16
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2808093-2
    ISSN 2198-3844 ; 2198-3844
    ISSN (online) 2198-3844
    ISSN 2198-3844
    DOI 10.1002/advs.202308447
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article ; Online: Immuno-engineered mRNA combined with cell adhesive niche for synergistic modulation of the MSC secretome.

    Drzeniek, Norman Michael / Kahwaji, Nourhan / Schlickeiser, Stephan / Reinke, Petra / Geißler, Sven / Volk, Hans-Dieter / Gossen, Manfred

    Biomaterials

    2022  Volume 294, Page(s) 121971

    Abstract: In vitro transcribed (IVT-)mRNA has entered center stage for vaccine development due to its immune co-stimulating properties. Given the widely demonstrated safety of IVT-mRNA-based vaccines, we aimed to adopt IVT-mRNA encoding VEGF for secretory ... ...

    Abstract In vitro transcribed (IVT-)mRNA has entered center stage for vaccine development due to its immune co-stimulating properties. Given the widely demonstrated safety of IVT-mRNA-based vaccines, we aimed to adopt IVT-mRNA encoding VEGF for secretory phenotype modulation of therapeutic cells. However, we observed that the immunogenicity of IVT-mRNA impairs the endogenous secretion of pro-angiogenic mediators from transfected mesenchymal stromal cells, instead inducing anti-angiogenic chemokines. This inflammatory secretome modulation limits the application potential of unmodified IVT-mRNA for cell therapy manufacturing, pro-angiogenic therapy and regenerative medicine. To uncouple immunogenicity from the protein expression functionality, we immuno-engineered IVT-mRNA with different chemically modified ribonucleotides. 5-Methoxy-uridine-modification of IVT-mRNA rescued the endogenous secretome pattern of transfected cells and prolonged secretion of IVT-mRNA-encoded VEGF. We found that high secretion of IVT-mRNA-encoded protein further depends on optimized cell adhesion. Cell encapsulation in a collagen-hyaluronic acid hydrogel increased secretion of IVT-mRNA-encoded VEGF and augmented the endogenous secretion of supporting pro-angiogenic mediators, such as HGF. Integrating minimally immunogenic mRNA technology with predesigned matrix-derived cues allows for the synergistic combination of multiple dimensions of cell manipulation and opens routes for biomaterial-based delivery of mRNA-engineered cell products. Such multimodal systems could present a more biologically relevant way to therapeutically address complex multifactorial processes such as tissue ischemia, angiogenesis, and regeneration.
    MeSH term(s) RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Vascular Endothelial Growth Factor A/genetics ; Vascular Endothelial Growth Factor A/metabolism ; Secretome ; Mesenchymal Stem Cells ; Regenerative Medicine/methods
    Chemical Substances RNA, Messenger ; Vascular Endothelial Growth Factor A
    Language English
    Publishing date 2022-12-26
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603079-8
    ISSN 1878-5905 ; 0142-9612
    ISSN (online) 1878-5905
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2022.121971
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article ; Online: MSC Therapies for COVID-19: Importance of Patient Coagulopathy, Thromboprophylaxis, Cell Product Quality and Mode of Delivery for Treatment Safety and Efficacy.

    Moll, Guido / Drzeniek, Norman / Kamhieh-Milz, Julian / Geissler, Sven / Volk, Hans-Dieter / Reinke, Petra

    Frontiers in immunology

    2020  Volume 11, Page(s) 1091

    Abstract: Numerous clinical trials of mesenchymal stromal/stem cells (MSCs) as a new treatment for coronavirus-induced disease (COVID-19) have been registered recently, most of them based on intravenous (IV) infusion. There is no approved effective therapy for ... ...

    Abstract Numerous clinical trials of mesenchymal stromal/stem cells (MSCs) as a new treatment for coronavirus-induced disease (COVID-19) have been registered recently, most of them based on intravenous (IV) infusion. There is no approved effective therapy for COVID-19, but MSC therapies have shown first promise in the treatment of acute respiratory distress syndrome (ARDS) pneumonia, inflammation, and sepsis, which are among the leading causes of mortality in COVID-19 patients. Many of the critically ill COVID-19 patients are in a hypercoagulable procoagulant state and at high risk for disseminated intravascular coagulation, thromboembolism, and thrombotic multi-organ failure, another cause of high fatality. It is not yet clear whether IV infusion is a safe and effective route of MSC delivery in COVID-19, since MSC-based products express variable levels of highly procoagulant tissue factor (TF/CD142), compromising the cells' hemocompatibility and safety profile. Of concern, IV infusions of poorly characterized MSC products with unchecked (high) TF/CD142 expression could trigger blood clotting in COVID-19 and other vulnerable patient populations and further promote the risk for thromboembolism. In contrast, well-characterized products with robust manufacturing procedures and optimized modes of clinical delivery hold great promise for ameliorating COVID-19 by exerting their beneficial immunomodulatory effects, inducing tissue repair and organ protection. While the need for MSC therapy in COVID-19 is apparent, integrating both innate and adaptive immune compatibility testing into the current guidelines for cell, tissue, and organ transplantation is critical for safe and effective therapies. It is paramount to only use well-characterized, safe MSCs even in the most urgent and experimental treatments. We here propose three steps to mitigate the risk for these vulnerable patients: (1) updated clinical guidelines for cell and tissue transplantation, (2) updated minimal criteria for characterization of cellular therapeutics, and (3) updated cell therapy routines reflecting specific patient needs.
    MeSH term(s) Administration, Intravenous ; Blood Coagulation Disorders/etiology ; COVID-19 ; Cell- and Tissue-Based Therapy/methods ; Coronavirus Infections/complications ; Coronavirus Infections/immunology ; Coronavirus Infections/therapy ; Guidelines as Topic ; Humans ; Injections, Intramuscular ; Mesenchymal Stem Cell Transplantation/adverse effects ; Mesenchymal Stem Cell Transplantation/methods ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/immunology ; Pneumonia, Viral/therapy ; Transplantation Immunology
    Keywords covid19
    Language English
    Publishing date 2020-05-19
    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.2020.01091
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article ; Online: Editorial comment: variables affecting the presence of mesenchymal stromal cells in the peripheral blood and their relationship with apheresis product.

    Moll, Guido / Drzeniek, Norman / Kamhieh-Milz, Julian / Geissler, Sven / Reinke, Petra

    British journal of haematology

    2020  Volume 189, Issue 4, Page(s) 593–596

    MeSH term(s) Blood Component Removal ; Granulocyte Colony-Stimulating Factor ; Hematopoietic Stem Cell Mobilization ; Humans ; Mesenchymal Stem Cells
    Chemical Substances Granulocyte Colony-Stimulating Factor (143011-72-7)
    Language English
    Publishing date 2020-02-10
    Publishing country England
    Document type Editorial ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.16389
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article ; Online: MSC Therapies for COVID-19

    Moll, Guido / Drzeniek, Norman / Kamhieh-Milz, Julian / Geissler, Sven / Volk, Hans-Dieter / Reinke, Petra

    Frontiers in Immunology

    Importance of Patient Coagulopathy, Thromboprophylaxis, Cell Product Quality and Mode of Delivery for Treatment Safety and Efficacy

    2020  Volume 11

    Keywords covid19
    Publisher Frontiers Media SA
    Publishing country ch
    Document type Article ; Online
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.01091
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  8. Article: MSC Therapies for COVID-19: Importance of Patient Coagulopathy, Thromboprophylaxis, Cell Product Quality and Mode of Delivery for Treatment Safety and Efficacy

    Moll, Guido / Drzeniek, Norman / Kamhieh-Milz, Julian / Geissler, Sven / Volk, Hans-Dieter / Reinke, Petra

    Front Immunol

    Abstract: Numerous clinical trials of mesenchymal stromal/stem cells (MSCs) as a new treatment for coronavirus-induced disease (COVID-19) have been registered recently, most of them based on intravenous (IV) infusion. There is no approved effective therapy for ... ...

    Abstract Numerous clinical trials of mesenchymal stromal/stem cells (MSCs) as a new treatment for coronavirus-induced disease (COVID-19) have been registered recently, most of them based on intravenous (IV) infusion. There is no approved effective therapy for COVID-19, but MSC therapies have shown first promise in the treatment of acute respiratory distress syndrome (ARDS) pneumonia, inflammation, and sepsis, which are among the leading causes of mortality in COVID-19 patients. Many of the critically ill COVID-19 patients are in a hypercoagulable procoagulant state and at high risk for disseminated intravascular coagulation, thromboembolism, and thrombotic multi-organ failure, another cause of high fatality. It is not yet clear whether IV infusion is a safe and effective route of MSC delivery in COVID-19, since MSC-based products express variable levels of highly procoagulant tissue factor (TF/CD142), compromising the cells' hemocompatibility and safety profile. Of concern, IV infusions of poorly characterized MSC products with unchecked (high) TF/CD142 expression could trigger blood clotting in COVID-19 and other vulnerable patient populations and further promote the risk for thromboembolism. In contrast, well-characterized products with robust manufacturing procedures and optimized modes of clinical delivery hold great promise for ameliorating COVID-19 by exerting their beneficial immunomodulatory effects, inducing tissue repair and organ protection. While the need for MSC therapy in COVID-19 is apparent, integrating both innate and adaptive immune compatibility testing into the current guidelines for cell, tissue, and organ transplantation is critical for safe and effective therapies. It is paramount to only use well-characterized, safe MSCs even in the most urgent and experimental treatments. We here propose three steps to mitigate the risk for these vulnerable patients: (1) updated clinical guidelines for cell and tissue transplantation, (2) updated minimal criteria for characterization of cellular therapeutics, and (3) updated cell therapy routines reflecting specific patient needs.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #589811
    Database COVID19

    Kategorien

  9. Article ; Online: Bio-instructive hydrogel expands the paracrine potency of mesenchymal stem cells.

    Drzeniek, Norman M / Mazzocchi, Andrea / Schlickeiser, Stephan / Forsythe, Steven D / Moll, Guido / Geißler, Sven / Reinke, Petra / Gossen, Manfred / Gorantla, Vijay S / Volk, Hans-Dieter / Soker, Shay

    Biofabrication

    2021  Volume 13, Issue 4

    Abstract: The therapeutic efficacy of clinically applied mesenchymal stromal cells (MSCs) is limited due to their injection into ... ...

    Abstract The therapeutic efficacy of clinically applied mesenchymal stromal cells (MSCs) is limited due to their injection into harsh
    MeSH term(s) Collagen Type I ; Endothelial Cells ; Humans ; Hyaluronic Acid ; Hydrogels ; Mesenchymal Stem Cells
    Chemical Substances Collagen Type I ; Hydrogels ; Hyaluronic Acid (9004-61-9)
    Language English
    Publishing date 2021-07-08
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2500944-8
    ISSN 1758-5090 ; 1758-5082
    ISSN (online) 1758-5090
    ISSN 1758-5082
    DOI 10.1088/1758-5090/ac0a32
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top