PMID- 24388817
OWN - NLM
STAT- MEDLINE
DCOM- 20140926
LR  - 20181202
IS  - 1878-5905 (Electronic)
IS  - 0142-9612 (Linking)
VI  - 35
IP  - 9
DP  - 2014 Mar
TI  - Substrate-mediated nanoparticle/gene delivery to MSC spheroids and their 
      applications in peripheral nerve regeneration.
PG  - 2630-41
LID - S0142-9612(13)01505-6 [pii]
LID - 10.1016/j.biomaterials.2013.12.021 [doi]
AB  - Substrate-derived mesenchymal stem cell (MSC) spheroids show greater 
      differentiation capacities than dispersed single cells in vitro. During spheroid 
      formation, nanoparticles (NPs)/genes may be delivered into the cells. In this 
      study, MSCs were conveniently labeled with superparamagnetic Fe3O4 NPs, or 
      transfected with brain-derived neurotrophic factor (BDNF) gene, by the 
      substrate-mediated NP/gene uptake. With the promising in vitro data showing the 
      beneficial effect on neural development and neurotrophic factor expression, MSCs 
      were combined with a polymeric nerve conduit to bridge a 10 mm transection gap of 
      rat sciatic nerve. High-resolution (7-T) magnetic resonance imaging (MRI) was 
      used to track the transplanted cells. Nerve regeneration was assessed by 
      functional recovery and histology. Results revealed that Fe3O4 NP-labeled MSCs 
      were successfully visualized by MRI in vivo. Animals receiving BDNF-transfected 
      MSC spheroids demonstrated the shortest gap bridging time (<21 days), the largest 
      regenerated nerve, and the thickest myelin sheath at 31 days. Compared to MSC 
      single cells, the pristine or BDNF-transfected MSC spheroids significantly 
      promoted the functional recovery of animals, especially for the BDNF-transfected 
      MSC spheroids. The transplanted MSCs were incorporated in the regenerated nerve 
      and differentiated into non-myelinating Schwann cells after 31 days. This study 
      suggests that the substrate-mediated gene delivery and NP labeling may provide 
      extra values for MSC spheroids to carry therapeutic/diagnostic agents in 
      cell-based therapy.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Tseng, Ting-Chen
AU  - Tseng TC
AD  - Institute of Polymer Science and Engineering, National Taiwan University, Taipei, 
      Taiwan.
FAU - Hsu, Shan-hui
AU  - Hsu SH
AD  - Institute of Polymer Science and Engineering, National Taiwan University, Taipei, 
      Taiwan; Research Center for Developmental Biology and Regenerative Medicine, 
      National Taiwan University, Taipei, Taiwan. Electronic address: shhsu@ntu.edu.tw.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140102
PL  - Netherlands
TA  - Biomaterials
JT  - Biomaterials
JID - 8100316
RN  - 0 (Chemokines)
RN  - 0 (Ferric Compounds)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Receptors, Chemokine)
RN  - 1K09F3G675 (ferric oxide)
SB  - IM
MH  - Animals
MH  - Chemokines/metabolism
MH  - Ferric Compounds/pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - *Gene Transfer Techniques
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/cytology/drug effects/*metabolism
MH  - Nanoparticles/*chemistry
MH  - Nerve Growth Factors/metabolism
MH  - *Nerve Regeneration/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Chemokine/metabolism
MH  - Recovery of Function/drug effects
MH  - Sciatic Nerve/drug effects/pathology/*physiopathology
MH  - Spheroids, Cellular/cytology/drug effects/*metabolism
MH  - Staining and Labeling
OTO - NOTNLM
OT  - Brain-derived neurotrophic factor (BDNF)
OT  - MSC spheroids
OT  - Peripheral nerve regeneration
OT  - Superparamagnetic iron oxide nanoparticles
EDAT- 2014/01/07 06:00
MHDA- 2014/09/27 06:00
CRDT- 2014/01/07 06:00
PHST- 2013/11/22 00:00 [received]
PHST- 2013/12/12 00:00 [accepted]
PHST- 2014/01/07 06:00 [entrez]
PHST- 2014/01/07 06:00 [pubmed]
PHST- 2014/09/27 06:00 [medline]
AID - S0142-9612(13)01505-6 [pii]
AID - 10.1016/j.biomaterials.2013.12.021 [doi]
PST - ppublish
SO  - Biomaterials. 2014 Mar;35(9):2630-41. doi: 10.1016/j.biomaterials.2013.12.021. 
      Epub 2014 Jan 2.