PMID- 28694020
OWN - NLM
STAT- MEDLINE
DCOM- 20180627
LR  - 20181202
IS  - 1347-4421 (Electronic)
IS  - 1347-4421 (Linking)
VI  - 124
IP  - 5
DP  - 2017 Nov
TI  - Transdifferentiation of brain-derived neurotrophic factor (BDNF)-secreting 
      mesenchymal stem cells significantly enhance BDNF secretion and Schwann cell 
      marker proteins.
PG  - 572-582
LID - S1389-1723(17)30039-7 [pii]
LID - 10.1016/j.jbiosc.2017.05.014 [doi]
AB  - The use of genetically modified mesenchymal stem cells (MSCs) is a rapidly 
      growing area of research targeting delivery of therapeutic factors for 
      neuro-repair. Cells can be programmed to hypersecrete various growth/trophic 
      factors such as brain-derived neurotrophic factor (BDNF), glial cell line-derived 
      neurotrophic factor (GDNF), and nerve growth factor (NGF) to promote regenerative 
      neurite outgrowth. In addition to genetic modifications, MSCs can be subjected to 
      transdifferentiation protocols to generate neural cell types to physically and 
      biologically support nerve regeneration. In this study, we have taken a novel 
      approach by combining these two unique strategies and evaluated the impact of 
      transdifferentiating genetically modified MSCs into a Schwann cell-like 
      phenotype. After 8 days in transdifferentiation media, approximately 30-50% of 
      transdifferentiated BDNF-secreting cells immunolabeled for Schwann cell markers 
      such as S100beta, S100, and p75(NTR). An enhancement was observed 20 days after 
      inducing transdifferentiation with minimal decreases in expression levels. BDNF 
      production was quantified by ELISA, and its biological activity tested via the 
      PC12-TrkB cell assay. Importantly, the bioactivity of secreted BDNF was verified 
      by the increased neurite outgrowth of PC12-TrkB cells. These findings demonstrate 
      that not only is BDNF actively secreted by the transdifferentiated BDNF-MSCs, but 
      also that it has the capacity to promote neurite sprouting and regeneration. 
      Given the fact that BDNF production remained stable for over 20 days, we believe 
      that these cells have the capacity to produce sustainable, effective, BDNF 
      concentrations over prolonged time periods and should be tested within an in vivo 
      system for future experiments.
CI  - Copyright (c) 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. 
      All rights reserved.
FAU - Bierlein De la Rosa, Metzere
AU  - Bierlein De la Rosa M
AD  - Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State 
      University, Ames, IA 50011, USA.
FAU - Sharma, Anup D
AU  - Sharma AD
AD  - Department of Chemical and Biological Engineering, Iowa State University, Ames, 
      IA 50011, USA; Neuroscience Program, Iowa State University, Ames, IA 50011, USA.
FAU - Mallapragada, Surya K
AU  - Mallapragada SK
AD  - Department of Chemical and Biological Engineering, Iowa State University, Ames, 
      IA 50011, USA; Neuroscience Program, Iowa State University, Ames, IA 50011, USA.
FAU - Sakaguchi, Donald S
AU  - Sakaguchi DS
AD  - Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State 
      University, Ames, IA 50011, USA; Department of Genetics, Development and Cell 
      Biology, Iowa State University, Ames, IA 50011, USA; Neuroscience Program, Iowa 
      State University, Ames, IA 50011, USA. Electronic address: dssakagu@iastate.edu.
LA  - eng
PT  - Journal Article
DEP - 20170708
PL  - Japan
TA  - J Biosci Bioeng
JT  - Journal of bioscience and bioengineering
JID - 100888800
RN  - 0 (Biomarkers)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Culture Media)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Biomarkers/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - *Cell Transdifferentiation/drug effects
MH  - Culture Media/pharmacology
MH  - Humans
MH  - Mesenchymal Stem Cells/*cytology/drug effects/*metabolism
MH  - Mice
MH  - Nerve Regeneration
MH  - Neurites/drug effects/physiology
MH  - PC12 Cells
MH  - Rats
MH  - Receptor, trkB/metabolism
MH  - Schwann Cells/*cytology/drug effects/*metabolism
OTO - NOTNLM
OT  - Brain-derived neurotrophic factor
OT  - Cellular area
OT  - High content screening
OT  - Mesenchymal stem cells
OT  - Morphometric analysis
OT  - Neurite outgrowth
OT  - Neuroprotection
OT  - Neuroregeneration
OT  - Peripheral nerve regeneration
OT  - Schwann cells
EDAT- 2017/07/12 06:00
MHDA- 2018/06/28 06:00
CRDT- 2017/07/12 06:00
PHST- 2017/01/17 00:00 [received]
PHST- 2017/05/09 00:00 [revised]
PHST- 2017/05/23 00:00 [accepted]
PHST- 2017/07/12 06:00 [pubmed]
PHST- 2018/06/28 06:00 [medline]
PHST- 2017/07/12 06:00 [entrez]
AID - S1389-1723(17)30039-7 [pii]
AID - 10.1016/j.jbiosc.2017.05.014 [doi]
PST - ppublish
SO  - J Biosci Bioeng. 2017 Nov;124(5):572-582. doi: 10.1016/j.jbiosc.2017.05.014. Epub 
      2017 Jul 8.