PMID- 29215199
OWN - NLM
STAT- MEDLINE
DCOM- 20190923
LR  - 20190923
IS  - 2157-6564 (Print)
IS  - 2157-6580 (Electronic)
IS  - 2157-6564 (Linking)
VI  - 7
IP  - 1
DP  - 2018 Jan
TI  - Neurotrophically Induced Mesenchymal Progenitor Cells Derived from Induced 
      Pluripotent Stem Cells Enhance Neuritogenesis via Neurotrophin and Cytokine 
      Production.
PG  - 45-58
LID - 10.1002/sctm.17-0108 [doi]
AB  - Adult tissue-derived mesenchymal stem cells (MSCs) are known to produce a number 
      of bioactive factors, including neurotrophic growth factors, capable of 
      supporting and improving nerve regeneration. However, with a finite culture 
      expansion capacity, MSCs are inherently limited in their lifespan and use. We 
      examined here the potential utility of an alternative, mesenchymal-like cell 
      source, derived from induced pluripotent stem cells, termed induced mesenchymal 
      progenitor cells (MiMPCs). We found that several genes were upregulated and 
      proteins were produced in MiMPCs that matched those previously reported for MSCs. 
      Like MSCs, the MiMPCs secreted various neurotrophic and neuroprotective factors, 
      including brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), 
      leukemia inhibitory factor (LIF), osteopontin, and osteonectin, and promoted 
      neurite outgrowth in chick embryonic dorsal root ganglia (DRG) cultures compared 
      with control cultures. Cotreatment with a pharmacological Trk-receptor inhibitor 
      did not result in significant decrease in MiMPC-induced neurite outgrowth, which 
      was however inhibited upon Jak/STAT3 blockade. These findings suggest that the 
      MiMPC induction of DRG neurite outgrowth is unlikely to be solely dependent on 
      BDNF, but instead Jak/STAT3 activation by IL-6 and/or LIF is likely to be 
      critical neurotrophic signaling pathways of the MiMPC secretome. Taken together, 
      these findings suggest MiMPCs as a renewable, candidate source of therapeutic 
      cells and a potential alternative to MSCs for peripheral nerve repair, in view of 
      their ability to promote nerve growth by producing many of the same growth 
      factors and cytokines as Schwann cells and signaling through critical 
      neurotrophic pathways. Stem Cells Translational Medicine 2018;7:45-58.
CI  - (c) 2017 The Authors Stem Cells Translational Medicine published by Wiley 
      Periodicals, Inc. on behalf of AlphaMed Press.
FAU - Brick, Rachel M
AU  - Brick RM
AD  - Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, 
      University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
AD  - Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, 
      Pennsylvania, USA.
FAU - Sun, Aaron X
AU  - Sun AX
AD  - Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, 
      University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
AD  - Department of Bioengineering, University of Pittsburgh Swanson School of 
      Engineering, Pittsburgh, Pennsylvania, USA.
FAU - Tuan, Rocky S
AU  - Tuan RS
AUID- ORCID: 0000-0001-6067-6705
AD  - Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, 
      University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
AD  - Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, 
      Pennsylvania, USA.
AD  - Department of Bioengineering, University of Pittsburgh Swanson School of 
      Engineering, Pittsburgh, Pennsylvania, USA.
LA  - eng
GR  - T32 EB001026/EB/NIBIB NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20171207
PL  - England
TA  - Stem Cells Transl Med
JT  - Stem cells translational medicine
JID - 101578022
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cytokines)
RN  - 0 (IL6 protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (LIF protein, human)
RN  - 0 (Leukemia Inhibitory Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Osteonectin)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Triterpenes)
RN  - 106441-73-0 (Osteopontin)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - SHQ47990PH (cucurbitacin I)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Line
MH  - Chick Embryo
MH  - Cytokines/*metabolism
MH  - Ganglia, Spinal/cytology/growth & development
MH  - Humans
MH  - Induced Pluripotent Stem Cells/cytology/*metabolism
MH  - Interleukin-6/metabolism
MH  - Leukemia Inhibitory Factor/metabolism
MH  - Mesenchymal Stem Cells/cytology/*metabolism
MH  - Nerve Growth Factors/*metabolism
MH  - Nerve Regeneration/*physiology
MH  - Neurites/metabolism
MH  - Neurogenesis/physiology
MH  - Osteonectin/metabolism
MH  - Osteopontin/metabolism
MH  - STAT3 Transcription Factor/antagonists & inhibitors
MH  - Schwann Cells/*metabolism
MH  - Triterpenes/pharmacology
PMC - PMC5746147
OTO - NOTNLM
OT  - Cytokines
OT  - Induced pluripotent stem cells
OT  - Mesenchymal stem cells
OT  - Nanofiber scaffold
OT  - Nerve growth
OT  - Nerve repair
OT  - Neurotrophins
OT  - Regenerative medicine
OT  - Sholl analysis
OT  - Tissue engineering
EDAT- 2017/12/08 06:00
MHDA- 2019/09/24 06:00
PMCR- 2017/12/07
CRDT- 2017/12/08 06:00
PHST- 2017/04/27 00:00 [received]
PHST- 2017/11/06 00:00 [accepted]
PHST- 2017/12/08 06:00 [pubmed]
PHST- 2019/09/24 06:00 [medline]
PHST- 2017/12/08 06:00 [entrez]
PHST- 2017/12/07 00:00 [pmc-release]
AID - SCT312256 [pii]
AID - 10.1002/sctm.17-0108 [doi]
PST - ppublish
SO  - Stem Cells Transl Med. 2018 Jan;7(1):45-58. doi: 10.1002/sctm.17-0108. Epub 2017 
      Dec 7.