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Pluronic Micelle-Me...
Pluronic Micelle-Mediated Tissue Factor Silencing Enhances Hemocompatibility, Stemness, Differentiation Potential, and Paracrine Signaling of Mesenchymal Stem Cells
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- Rangasami, Vignesh K. (författare)
- Tampere Univ, Fac Med & Hlth Technol, Bioengn & Nanomed Grp, Tampere 33720, Finland.
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- Nawale, Ganesh N. (författare)
- Uppsala universitet,Polymerkemi,Translational Chemical Biology Laboratory
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- Asawa, Kenta (författare)
- Univ Tokyo, Dept Bioengn, Bunkyo Ku, Tokyo 1138656, Japan.
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- Kadekar, Sandeep (författare)
- Uppsala universitet,Polymerkemi,Translational Chemical Biology Laboratory
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- Samanta, Sumanta (författare)
- Tampere Univ, Fac Med & Hlth Technol, Bioengn & Nanomed Grp, Tampere 33720, Finland.
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- Nilsson, Bo (författare)
- Uppsala universitet,Klinisk immunologi
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- Nilsson Ekdahl, Kristina (författare)
- Uppsala universitet,Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Avancerade material,Uppsala University, Sweden,Linnaeus Ctr Biomat Chem, BMC,Klinisk immunologi,Linnaeus Univ, Fac Hlth & Life Sci, Dept Chem & Biomed Sci, SE-39182 Kalmar, Sweden.
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- Miettinen, Susanna (författare)
- Tampere Univ, Fac Med & Hlth Technol, Adult Stem Cells Grp, Tampere 33014, Finland.;Tampere Univ Hosp, Res Dev & Innovat Ctr, Tampere 33520, Finland.
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- Hilborn, Jöns, 1956- (författare)
- Uppsala universitet,Polymerkemi
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- Teramura, Yuji (författare)
- Uppsala universitet,Klinisk immunologi,Univ Tokyo, Dept Bioengn, Bunkyo Ku, Tokyo 1138656, Japan.
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- Varghese, Oommen P. (författare)
- Univ Tokyo, Dept Bioengn, Bunkyo Ku, Tokyo 1138656, Japan.
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- Oommen, Oommen P. (författare)
- Tampere Univ, Fac Med & Hlth Technol, Bioengn & Nanomed Grp, Tampere 33720, Finland.
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Tampere Univ, Fac Med & Hlth Technol, Bioengn & Nanomed Grp, Tampere 33720, Finland Polymerkemi (creator_code:org_t)
- 2021-04-05
- 2021
- Engelska.
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 22:5, s. 1980-1989
- Relaterad länk:
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https://doi.org/10.1...
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https://pubs.acs.org...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- 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 similar to 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Nyckelord
- Biomedical Sciences
- Biomedicinsk vetenskap
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Rangasami, Vigne ...
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Nawale, Ganesh N ...
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Asawa, Kenta
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Kadekar, Sandeep
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Samanta, Sumanta
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Nilsson, Bo
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Nilsson Ekdahl, ...
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Miettinen, Susan ...
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Hilborn, Jöns, 1 ...
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Teramura, Yuji
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Varghese, Oommen ...
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Oommen, Oommen P ...
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Linnéuniversitetet
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Uppsala universitet