PMID- 19322031
OWN - NLM
STAT- MEDLINE
DCOM- 20090904
LR  - 20211020
IS  - 1226-3613 (Print)
IS  - 1226-3613 (Linking)
VI  - 41
IP  - 7
DP  - 2009 Jul 31
TI  - Growth factor-expressing human neural progenitor cell grafts protect motor 
      neurons but do not ameliorate motor performance and survival in ALS mice.
PG  - 487-500
LID - 10.3858/emm.2009.41.7.054 [doi]
AB  - Neural progenitor cells (NPs) have shown several promising benefits for the 
      treatment of neurological disorders. To evaluate the therapeutic potential of 
      human neural progenitor cells (hNPs) in amyotrophic lateral sclerosis (ALS), we 
      transplanted hNPs or growth factor (GF)-expressing hNPs into the central nervous 
      system (CNS) of mutant Cu/Zn superoxide dismutase (SOD1(G93A)) transgenic mice. 
      The hNPs were engineered to express brain-derived neurotrophic factor (BDNF), 
      insulin-like growth factor-1 (IGF-1), VEGF, neurotrophin-3 (NT-3), or glial 
      cell-derived neurotrophic factor (GDNF), respectively, by adenoviral vector and 
      GDNF by lentiviral vector before transplantation. Donor-derived cells engrafted 
      and migrated into the spinal cord or brain of ALS mice and differentiated into 
      neurons, oligodendrocytes, or glutamate transporter-1 (GLT1)-expressing 
      astrocytes while some cells retained immature markers. Transplantation of GDNF- 
      or IGF-1-expressing hNPs attenuated the loss of motor neurons and induced trophic 
      changes in motor neurons of the spinal cord. However, improvement in motor 
      performance and extension of lifespan were not observed in all hNP 
      transplantation groups compared to vehicle-injected controls. Moreover, the 
      lifespan of GDNF-expressing hNP recipient mice by lentiviral vector was shortened 
      compared to controls, which was largely due to the decreased survival times of 
      female animals. These results imply that although implanted hNPs differentiate 
      into GLT1-expressing astrocytes and secrete GFs, which maintain dying motor 
      neurons, inadequate trophic support could be harmful and there is sexual 
      dimorphism in response to GDNF delivery in ALS mice. Therefore, additional 
      therapeutic approaches may be required for full functional recovery.
FAU - Park, Sungju
AU  - Park S
AD  - Department of Pediatrics, Yonsei University College of Medicine, Seoul 120-752, 
      Korea.
FAU - Kim, Hyoung-Tae
AU  - Kim HT
FAU - Yun, Seokkwan
AU  - Yun S
FAU - Kim, Il-Sun
AU  - Kim IS
FAU - Lee, Jiyoon
AU  - Lee J
FAU - Lee, Il-Shin
AU  - Lee IS
FAU - Park, Kook In
AU  - Park KI
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Exp Mol Med
JT  - Experimental & molecular medicine
JID - 9607880
RN  - 0 (Excitatory Amino Acid Transporter 2)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (SOD1 protein, human)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 1.15.1.1 (Sod1 protein, mouse)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.15.1.1 (Superoxide Dismutase-1)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Amyotrophic Lateral Sclerosis/metabolism/mortality/*therapy
MH  - Animals
MH  - Astrocytes/metabolism
MH  - Brain/*embryology
MH  - Cell Differentiation
MH  - Disease Models, Animal
MH  - Excitatory Amino Acid Transporter 2/metabolism
MH  - Female
MH  - Fetal Stem Cells/*metabolism
MH  - Genetic Vectors
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Motor Neurons/*physiology
MH  - Nerve Growth Factors/*metabolism
MH  - *Stem Cell Transplantation
MH  - Superoxide Dismutase/genetics
MH  - Superoxide Dismutase-1
MH  - Transfection
MH  - Vascular Endothelial Growth Factor A/genetics/metabolism
PMC - PMC2721146
EDAT- 2009/03/27 09:00
MHDA- 2009/09/05 06:00
PMCR- 2009/07/31
CRDT- 2009/03/27 09:00
PHST- 2009/03/27 09:00 [entrez]
PHST- 2009/03/27 09:00 [pubmed]
PHST- 2009/09/05 06:00 [medline]
PHST- 2009/07/31 00:00 [pmc-release]
AID - 10.3858/emm.2009.41.7.054 [doi]
PST - ppublish
SO  - Exp Mol Med. 2009 Jul 31;41(7):487-500. doi: 10.3858/emm.2009.41.7.054.