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  • Rangasami, Vignesh K.Tampere Univ, Fac Med & Hlth Technol, Bioengn & Nanomed Grp, Tampere 33720, Finland. (author)

Pluronic Micelle-Mediated Tissue Factor Silencing Enhances Hemocompatibility, Stemness, Differentiation Potential, and Paracrine Signaling of Mesenchymal Stem Cells

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-04-05
  • American Chemical Society (ACS),2021
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:lnu-104523
  • https://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-104523URI
  • https://doi.org/10.1021/acs.biomac.1c00070DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-445583URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Nawale, Ganesh N.Uppsala universitet,Polymerkemi,Translational Chemical Biology Laboratory(Swepub:uu)ganna194 (author)
  • Asawa, KentaUniv Tokyo, Dept Bioengn, Bunkyo Ku, Tokyo 1138656, Japan. (author)
  • Kadekar, SandeepUppsala universitet,Polymerkemi,Translational Chemical Biology Laboratory(Swepub:uu)sanka861 (author)
  • Samanta, SumantaTampere Univ, Fac Med & Hlth Technol, Bioengn & Nanomed Grp, Tampere 33720, Finland. (author)
  • Nilsson, BoUppsala universitet,Klinisk immunologi(Swepub:uu)bonils (author)
  • Nilsson Ekdahl, KristinaUppsala 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.(Swepub:uu)krisnil (author)
  • Miettinen, SusannaTampere Univ, Fac Med & Hlth Technol, Adult Stem Cells Grp, Tampere 33014, Finland.;Tampere Univ Hosp, Res Dev & Innovat Ctr, Tampere 33520, Finland. (author)
  • Hilborn, Jöns,1956-Uppsala universitet,Polymerkemi(Swepub:uu)johil255 (author)
  • Teramura, YujiUppsala universitet,Klinisk immunologi,Univ Tokyo, Dept Bioengn, Bunkyo Ku, Tokyo 1138656, Japan.(Swepub:uu)yujte186 (author)
  • Varghese, Oommen P.Univ Tokyo, Dept Bioengn, Bunkyo Ku, Tokyo 1138656, Japan. (author)
  • Oommen, Oommen P.Tampere Univ, Fac Med & Hlth Technol, Bioengn & Nanomed Grp, Tampere 33720, Finland. (author)
  • Tampere Univ, Fac Med & Hlth Technol, Bioengn & Nanomed Grp, Tampere 33720, Finland.Polymerkemi (creator_code:org_t)

Related titles

  • In:Biomacromolecules: American Chemical Society (ACS)22:5, s. 1980-19891525-77971526-4602

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