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Gregor Fuhrmann

Bio: Gregor Fuhrmann is an academic researcher from Saarland University. The author has contributed to research in topics: Cytotoxicity & Vesicle. The author has an hindex of 1, co-authored 2 publications receiving 20 citations. Previous affiliations of Gregor Fuhrmann include University of Erlangen-Nuremberg.

Papers
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Journal ArticleDOI
TL;DR: In this paper, the authors discuss the biological role of extracellular vesicles and how they can be applied as drug carriers, focusing on the current state of their manufacturing and existing challenges.
Abstract: Extracellular-vesicle-based cell-to-cell communication is conserved across all kingdoms of life. There is compelling evidence that extracellular vesicles are involved in major (patho)physiological processes, including cellular homoeostasis, infection propagation, cancer development and cardiovascular diseases. Various studies suggest that extracellular vesicles have several advantages over conventional synthetic carriers, opening new frontiers for modern drug delivery. Despite extensive research, clinical translation of extracellular-vesicle-based therapies remains challenging. Here, we discuss the uniqueness of extracellular vesicles along with critical design and development steps required to utilize their full potential as drug carriers, including loading methods, in-depth characterization and large-scale manufacturing. We compare the prospects of extracellular vesicles with those of the well established liposomes and provide guidelines to direct the process of developing vesicle-based drug delivery systems. In this Review the authors discuss the biological role of extracellular vesicles and how they can be applied as drug carriers, focusing on the current state of their manufacturing and existing challenges.

481 citations

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TL;DR: In this article, the authors compared the performance of pneumococcal membrane vesicles (MVs) with stationary-phase and death-phase vesicle types, and found that the death phase MVs produced higher yields than the stationary phase.
Abstract: Streptococcus pneumoniae infections are a leading cause of death worldwide. Bacterial membrane vesicles (MVs) are promising vaccine candidates because of the antigenic components of their parent microorganisms. Pneumococcal MVs exhibit low toxicity towards several cell lines, but their clinical translation requires a high yield and strong immunogenic effects without compromising immune cell viability. MVs are isolated during either the stationary phase (24 h) or death phase (48 h), and their yields, immunogenicity and cytotoxicity in human primary macrophages and dendritic cells have been investigated. Death-phase vesicles showed higher yields than stationary-phase vesicles. Both vesicle types displayed acceptable compatibility with primary immune cells and several cell lines. Both vesicle types showed comparable uptake and enhanced release of the inflammatory cytokines, tumor necrosis factor and interleukin-6, from human primary immune cells. Proteomic analysis revealed similarities in vesicular immunogenic proteins such as pneumolysin, pneumococcal surface protein A, and IgA1 protease in both vesicle types, but stationary-phase MVs showed significantly lower autolysin levels than death-phase MVs. Although death-phase vesicles produced higher yields, they lacked superiority to stationary-phase vesicles as vaccine candidates owing to their similar antigenic protein cargo and comparable uptake into primary human immune cells.

8 citations


Cited by
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TL;DR: A review of RNA therapeutic classes, their molecular mechanisms of action, and the design considerations for their respective delivery platforms can be found in this paper , where the authors discuss the path from preclinical drug delivery research to clinical approval of these drugs.
Abstract: RNA-based gene therapy requires therapeutic RNA to function inside target cells without eliciting unwanted immune responses. RNA can be ferried into cells using non-viral drug delivery systems, which circumvent the limitations of viral delivery vectors. Here, we review the growing number of RNA therapeutic classes, their molecular mechanisms of action, and the design considerations for their respective delivery platforms. We describe polymer-based, lipid-based, and conjugate-based drug delivery systems, differentiating between those that passively and those that actively target specific cell types. Finally, we describe the path from preclinical drug delivery research to clinical approval, highlighting opportunities to improve the efficiency with which new drug delivery systems are discovered. RNA therapies can be used to manipulate gene expression or produce therapeutic proteins. Here, the authors describe the growing number of RNA therapies and their molecular mechanisms of action. They also discuss the path from preclinical drug delivery research to clinical approval of these drugs.

202 citations

Journal ArticleDOI
Zhijie Weng1, Bowen Zhang1, Chenzhou Wu1, Fanyuan Yu1, Bo Han1, Bo Li1, Longjiang Li1 
TL;DR: In this paper, mesenchymal stem cells (MSCs) could either support or suppress tumor progression in different cancers by paracrine signaling via MSC-derived extracellular vesicles.
Abstract: Extracellular vesicles (EVs) are cell-derived membrane structures enclosing proteins, lipids, RNAs, metabolites, growth factors, and cytokines. EVs have emerged as essential intercellular communication regulators in multiple physiological and pathological processes. Previous studies revealed that mesenchymal stem cells (MSCs) could either support or suppress tumor progression in different cancers by paracrine signaling via MSC-derived EVs. Evidence suggested that MSC-derived EVs could mimic their parental cells, possessing pro-tumor and anti-tumor effects, and inherent tumor tropism. Therefore, MSC-derived EVs can be a cell-free cancer treatment alternative. This review discusses different insights regarding MSC-derived EVs' roles in cancer treatment and summarizes bioengineered MSC-derived EVs' applications as safe and versatile anti-tumor agent delivery platforms. Meanwhile, current hurdles of moving MSC-derived EVs from bench to bedside are also discussed.

76 citations

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TL;DR: In this paper , a review of the potential of exosomes in the drug delivery system is presented, and the current challenges and potential directions of this new area of drug delivery are also investigated.

64 citations

Journal ArticleDOI
TL;DR: In this paper , the authors provide a snapshot of nanomedicines that have been currently launched or in the clinical trials, which manifests a diversified trend in carrier types, applied indications and mechanisms of action.

60 citations

Journal ArticleDOI
Qizhou Lian1
04 Jul 2022
TL;DR: In this paper , Mesenchymal stem cells (MSCs) have been widely isolated from various tissues including bone marrow, umbilical cord, and adipose tissue, with the potential for self-renewal and multipotent differentiation.
Abstract: Abstract Mesenchymal stem cells (MSCs) can be widely isolated from various tissues including bone marrow, umbilical cord, and adipose tissue, with the potential for self-renewal and multipotent differentiation. There is compelling evidence that the therapeutic effect of MSCs mainly depends on their paracrine action. Extracellular vesicles (EVs) are fundamental paracrine effectors of MSCs and play a crucial role in intercellular communication, existing in various body fluids and cell supernatants. Since MSC-derived EVs retain the function of protocells and have lower immunogenicity, they have a wide range of prospective therapeutic applications with advantages over cell therapy. We describe some characteristics of MSC-EVs, and discuss their role in immune regulation and regeneration, with emphasis on the molecular mechanism and application of MSC-EVs in the treatment of fibrosis and support tissue repair. We also highlight current challenges in the clinical application of MSC-EVs and potential ways to overcome the problem of quality heterogeneity.

50 citations