PMID- 26546037
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20181202
IS  - 1435-1463 (Electronic)
IS  - 0300-9564 (Linking)
VI  - 123
IP  - 3
DP  - 2016 Mar
TI  - Neonatal human retinal pigment epithelial cells secrete limited trophic factors 
      in vitro and in vivo following striatal implantation in parkinsonian rats.
PG  - 167-77
LID - 10.1007/s00702-015-1480-7 [doi]
AB  - Human retinal pigment epithelial (hRPE) cell implants into the striatum have been 
      investigated as a potential cell-based treatment for Parkinson's disease in a 
      Phase II clinical trial that recently failed. We hypothesize that the trophic 
      factor potential of the hRPE cells could potentially influence the function 
      and/or survival of the implants and may be involved in an alternative mechanism 
      of action. However, it is unclear if hRPE cells secreted trophic factors when 
      handled in the manner used in the clinical Phase II trial. To address these 
      questions, we investigated two neonatal hRPE cell lots, cultured in a similar 
      manner to hRPE cells used in a Phase II clinical study, and longitudinally 
      determined brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 
      (FGF2), and pigment epithelium-derived factor concentrations in vitro and 
      following striatal implantation into 6-hydroxydopamine-lesioned rats. The results 
      demonstrate short-lived BDNF and FGF2 concentrations in vitro from hRPE cells 
      grown alone or attached to gelatin microcarriers (GM)s as well as limited trophic 
      factor concentration differences in vivo following striatal implantation of 
      hRPE-GM in 6-hydroxydopamine lesioned rats compared to sham (GM-only). The data 
      suggest that trophic factors from neonatal hRPE cell implants likely did not 
      participate in an alternative mechanism of action, which adds supports to a 
      hypothesis that additional factors may have been necessary for the survival 
      and/or function of hRPE implants and potentially the success of the Phase II 
      clinical trial.
FAU - Russ, Kaspar
AU  - Russ K
AD  - Pacific Parkinson's Research Centre, University of British Columbia, 2211 
      Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada. kruss1@interchange.ubc.ca.
AD  - Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg 
      Hospital, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark. 
      kruss1@interchange.ubc.ca.
FAU - Flores, Joseph
AU  - Flores J
AD  - Pacific Parkinson's Research Centre, University of British Columbia, 2211 
      Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada.
FAU - Brudek, Tomasz
AU  - Brudek T
AD  - Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg 
      Hospital, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark.
FAU - Doudet, Doris
AU  - Doudet D
AD  - Pacific Parkinson's Research Centre, University of British Columbia, 2211 
      Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151106
PL  - Austria
TA  - J Neural Transm (Vienna)
JT  - Journal of neural transmission (Vienna, Austria : 1996)
JID - 9702341
RN  - 0 (Nerve Growth Factors)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - *Clinical Trials, Phase II as Topic
MH  - Corpus Striatum/*surgery
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Humans
MH  - Infant, Newborn
MH  - Male
MH  - Nerve Growth Factors/*metabolism
MH  - Parkinsonian Disorders/*surgery
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Retinal Pigment Epithelium/cytology/metabolism/*transplantation
OTO - NOTNLM
OT  - 6-Hydroxydopamine
OT  - Cell transplantation
OT  - Levodopa
OT  - Neonatal
OT  - Parkinson's disease
OT  - Retinal pigment epithelial cells
OT  - Trophic factors
EDAT- 2015/11/08 06:00
MHDA- 2016/12/15 06:00
CRDT- 2015/11/08 06:00
PHST- 2015/08/21 00:00 [received]
PHST- 2015/10/23 00:00 [accepted]
PHST- 2015/11/08 06:00 [entrez]
PHST- 2015/11/08 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - 10.1007/s00702-015-1480-7 [pii]
AID - 10.1007/s00702-015-1480-7 [doi]
PST - ppublish
SO  - J Neural Transm (Vienna). 2016 Mar;123(3):167-77. doi: 10.1007/s00702-015-1480-7. 
      Epub 2015 Nov 6.