PMID- 19733542
OWN - NLM
STAT- MEDLINE
DCOM- 20091104
LR  - 20181201
IS  - 1875-9777 (Electronic)
IS  - 1875-9777 (Linking)
VI  - 5
IP  - 3
DP  - 2009 Sep 4
TI  - Neuroprotection of host cells by human central nervous system stem cells in a 
      mouse model of infantile neuronal ceroid lipofuscinosis.
PG  - 310-9
LID - 10.1016/j.stem.2009.05.022 [doi]
AB  - Infantile neuronal ceroid lipofuscinosis (INCL) is a fatal neurodegenerative 
      disease caused by a deficiency in the lysosomal enzyme palmitoyl protein 
      thioesterase-1 (PPT1). Ppt1 knockout mice display hallmarks of INCL and mimic the 
      human pathology: accumulation of lipofuscin, degeneration of CNS neurons, and a 
      shortened life span. Purified non-genetically modified human CNS stem cells, 
      grown as neurospheres (hCNS-SCns), were transplanted into the brains of 
      immunodeficient Ppt1(-/)(-) mice where they engrafted robustly, migrated 
      extensively, and produced sufficient levels of PPT1 to alter host neuropathology. 
      Grafted mice displayed reduced autofluorescent lipofuscin, significant 
      neuroprotection of host hippocampal and cortical neurons, and delayed loss of 
      motor coordination. Early intervention with cellular transplants of hCNS-SCns 
      into the brains of INCL patients may supply a continuous and long-lasting source 
      of the missing PPT1 and provide some therapeutic benefit through protection of 
      endogenous neurons. These data provide the experimental basis for human clinical 
      trials with these banked hCNS-SCns.
FAU - Tamaki, Stanley J
AU  - Tamaki SJ
AD  - StemCells, Inc., Palo Alto, CA 94304, USA.
FAU - Jacobs, Yakop
AU  - Jacobs Y
FAU - Dohse, Monika
AU  - Dohse M
FAU - Capela, Alexandra
AU  - Capela A
FAU - Cooper, Jonathan D
AU  - Cooper JD
FAU - Reitsma, Michael
AU  - Reitsma M
FAU - He, Dongping
AU  - He D
FAU - Tushinski, Robert
AU  - Tushinski R
FAU - Belichenko, Pavel V
AU  - Belichenko PV
FAU - Salehi, Ahmad
AU  - Salehi A
FAU - Mobley, William
AU  - Mobley W
FAU - Gage, Fred H
AU  - Gage FH
FAU - Huhn, Stephen
AU  - Huhn S
FAU - Tsukamoto, Ann S
AU  - Tsukamoto AS
FAU - Weissman, Irving L
AU  - Weissman IL
FAU - Uchida, Nobuko
AU  - Uchida N
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cell Stem Cell
JT  - Cell stem cell
JID - 101311472
RN  - 0 (Lipofuscin)
RN  - 0 (Receptor, IGF Type 2)
RN  - EC 3.1.2.- (Thiolester Hydrolases)
RN  - EC 3.1.2.22 (palmitoyl-protein thioesterase)
SB  - IM
MH  - Animals
MH  - Brain/enzymology/pathology
MH  - Cell Differentiation
MH  - Cell Movement
MH  - Cell Survival
MH  - Central Nervous System/*cytology
MH  - *Cytoprotection
MH  - Disease Models, Animal
MH  - Endocytosis
MH  - Fibroblasts/cytology/enzymology
MH  - Fluorescence
MH  - Humans
MH  - Inflammation/complications/pathology
MH  - Intracellular Space/enzymology
MH  - Lipofuscin/metabolism
MH  - Mice
MH  - Motor Activity
MH  - Mutation/genetics
MH  - Nerve Degeneration/complications/pathology/physiopathology
MH  - Neuronal Ceroid-Lipofuscinoses/complications/*pathology/physiopathology/*therapy
MH  - Neurons/*cytology/enzymology
MH  - Receptor, IGF Type 2/metabolism
MH  - Stem Cell Transplantation
MH  - Stem Cells/*cytology/metabolism
MH  - Thiolester Hydrolases/deficiency/metabolism
EDAT- 2009/09/08 06:00
MHDA- 2009/11/05 06:00
CRDT- 2009/09/08 06:00
PHST- 2007/11/28 00:00 [received]
PHST- 2008/09/23 00:00 [revised]
PHST- 2009/05/20 00:00 [accepted]
PHST- 2009/09/08 06:00 [entrez]
PHST- 2009/09/08 06:00 [pubmed]
PHST- 2009/11/05 06:00 [medline]
AID - S1934-5909(09)00231-8 [pii]
AID - 10.1016/j.stem.2009.05.022 [doi]
PST - ppublish
SO  - Cell Stem Cell. 2009 Sep 4;5(3):310-9. doi: 10.1016/j.stem.2009.05.022.