Pluronic Micelle-Mediated Tissue Factor Silencing Enhances Hemocompatibility, Stemness, Differentiation Potential, and Paracrine Signaling of Mesenchymal Stem Cells
| Autor: | Vignesh K. Rangasami, Sumanta Samanta, Yuji Teramura, Kristina Nilsson Ekdahl, Jöns Hilborn, Oommen P. Oommen, Kenta Asawa, Oommen P. Varghese, Ganesh N. Nawale, Susanna Miettinen, Bo Nilsson, Sandeep Kadekar |
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| Přispěvatelé: | Tampere University, BioMediTech, Tays Research Services |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Stromal cell
Polymers and Plastics Cellular differentiation Cell- och molekylärbiologi Biomaterialvetenskap Paracrine Communication Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology) Molecular Biology Microbiology Biochemistry or Biopharmacy) Bioengineering Inflammation 02 engineering and technology Poloxamer 010402 general chemistry 01 natural sciences Article Thromboplastin Biomaterials Paracrine signalling Tissue factor Materials Chemistry medicine Gene silencing Humans Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi) molekylärbiologi mikrobiologi biokemi eller biofarmaci) Cells Cultured Micelles Polymer Technologies Chemistry Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells 021001 nanoscience & nanotechnology Polymerteknologi 0104 chemical sciences Cell biology Biomaterials Science 3111 Biomedicine medicine.symptom 0210 nano-technology Cell and Molecular Biology |
| Zdroj: | Biomacromolecules |
| Popis: | Mesenchymal stem/stromal cells (MSCs) evoke great excitement for treating different human diseases due to their ability to home inflamed tissues, suppress inflammation, and promote tissue regeneration. Despite great promises, clinical trial results are disappointing as allotransplantation of MSCs trigger thrombotic activity and are damaged by the complement system, compromising their survival and function. To overcome this, a new strategy is presented by the silencing of tissue factor (TF), a transmembrane protein that mediates procoagulant activity. Novel Pluronic-based micelles are designed with the pendant pyridyl disulfide group, which are used to conjugate TF-targeting siRNA by the thiol-exchange reaction. This nanocarrier design effectively delivered the payload to MSCs resulting in ∼72% TF knockdown (KD) without significant cytotoxicity. Hematological evaluation of MSCs and TF-KD MSCs in an ex vivo human whole blood model revealed a significant reduction in an instant-blood-mediated-inflammatory reaction as evidenced by reduced platelet aggregation (93% of free platelets in the TF-KD group, compared to 22% in untreated bone marrow-derived MSCs) and thrombin-antithrombin complex formation. Effective TF silencing induced higher MSC differentiation in osteogenic and adipogenic media and showed stronger paracrine suppression of proinflammatory cytokines in macrophages and higher stimulation in the presence of endotoxins. Thus, TF silencing can produce functional cells with higher fidelity, efficacy, and functions. publishedVersion |
| Databáze: | OpenAIRE |
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