PMID- 33813822
OWN - NLM
STAT- MEDLINE
DCOM- 20210708
LR  - 20210708
IS  - 1526-4602 (Electronic)
IS  - 1525-7797 (Print)
IS  - 1525-7797 (Linking)
VI  - 22
IP  - 5
DP  - 2021 May 10
TI  - Pluronic Micelle-Mediated Tissue Factor Silencing Enhances Hemocompatibility, 
      Stemness, Differentiation Potential, and Paracrine Signaling of Mesenchymal Stem 
      Cells.
PG  - 1980-1989
LID - 10.1021/acs.biomac.1c00070 [doi]
AB  - 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  approximately 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.
FAU - Rangasami, Vignesh K
AU  - Rangasami VK
AD  - Bioengineering and Nanomedicine Group, Faculty of Medicine and Health 
      Technologies, Tampere University, Tampere 33720, Finland.
FAU - Nawale, Ganesh
AU  - Nawale G
AUID- ORCID: 0000-0002-7256-0758
AD  - Translational Chemical Biology Laboratory, Department of Chemistry, Angstrom 
      Laboratory, Uppsala University, Uppsala 751 21, Sweden.
FAU - Asawa, Kenta
AU  - Asawa K
AD  - Department of Bioengineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 
      Tokyo 113-8656, Japan.
FAU - Kadekar, Sandeep
AU  - Kadekar S
AD  - Translational Chemical Biology Laboratory, Department of Chemistry, Angstrom 
      Laboratory, Uppsala University, Uppsala 751 21, Sweden.
FAU - Samanta, Sumanta
AU  - Samanta S
AD  - Bioengineering and Nanomedicine Group, Faculty of Medicine and Health 
      Technologies, Tampere University, Tampere 33720, Finland.
FAU - Nilsson, Bo
AU  - Nilsson B
AD  - Department of Immunology, Genetics, and Pathology, Rudbeck Laboratory, Uppsala 
      University, Uppsala SE-75105, Sweden.
FAU - Ekdahl, Kristina N
AU  - Ekdahl KN
AD  - Department of Immunology, Genetics, and Pathology, Rudbeck Laboratory, Uppsala 
      University, Uppsala SE-75105, Sweden.
AD  - Department of Chemistry and Biomedical Sciences, Faculty of Health and Life 
      Sciences, Linnaeus University, Kalmar SE-391 82, Sweden.
FAU - Miettinen, Susanna
AU  - Miettinen S
AD  - Adult Stem Cells Group, Faculty of Medicine and Health Technologies, Tampere 
      University, Tampere 33014, Finland.
AD  - Research, Development and Innovation Center, Tampere University Hospital, Tampere 
      33520, Finland.
FAU - Hilborn, Jons
AU  - Hilborn J
AD  - Polymer Chemistry, Department of Chemistry-Angstrom Laboratory, Uppsala 
      University, Uppsala 751 21, Sweden.
FAU - Teramura, Yuji
AU  - Teramura Y
AUID- ORCID: 0000-0002-0709-1000
AD  - Department of Bioengineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 
      Tokyo 113-8656, Japan.
AD  - Department of Immunology, Genetics, and Pathology, Rudbeck Laboratory, Uppsala 
      University, Uppsala SE-75105, Sweden.
FAU - Varghese, Oommen P
AU  - Varghese OP
AUID- ORCID: 0000-0001-8872-9928
AD  - Department of Bioengineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 
      Tokyo 113-8656, Japan.
FAU - Oommen, Oommen P
AU  - Oommen OP
AUID- ORCID: 0000-0003-2768-0133
AD  - Bioengineering and Nanomedicine Group, Faculty of Medicine and Health 
      Technologies, Tampere University, Tampere 33720, Finland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210405
PL  - United States
TA  - Biomacromolecules
JT  - Biomacromolecules
JID - 100892849
RN  - 0 (Micelles)
RN  - 106392-12-5 (Poloxamer)
RN  - 9035-58-9 (Thromboplastin)
SB  - IM
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Humans
MH  - *Mesenchymal Stem Cells
MH  - Micelles
MH  - Paracrine Communication
MH  - Poloxamer
MH  - Thromboplastin/genetics
PMC - PMC8154246
COIS- The authors declare no competing financial interest.
EDAT- 2021/04/06 06:00
MHDA- 2021/07/09 06:00
PMCR- 2021/05/26
CRDT- 2021/04/05 05:20
PHST- 2021/04/06 06:00 [pubmed]
PHST- 2021/07/09 06:00 [medline]
PHST- 2021/04/05 05:20 [entrez]
PHST- 2021/05/26 00:00 [pmc-release]
AID - 10.1021/acs.biomac.1c00070 [doi]
PST - ppublish
SO  - Biomacromolecules. 2021 May 10;22(5):1980-1989. doi: 10.1021/acs.biomac.1c00070. 
      Epub 2021 Apr 5.