PMID- 15469951
OWN - NLM
STAT- MEDLINE
DCOM- 20050118
LR  - 20161124
IS  - 1460-2156 (Electronic)
IS  - 0006-8950 (Linking)
VI  - 127
IP  - Pt 11
DP  - 2004 Nov
TI  - Wild-type bone marrow cells ameliorate the phenotype of SOD1-G93A ALS mice and 
      contribute to CNS, heart and skeletal muscle tissues.
PG  - 2518-32
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive, lethal neurodegenerative 
      disease without any effective therapy. To evaluate the potential of wild-type 
      bone marrow (BM)-derived stem cells to modify the ALS phenotype, we generated BM 
      chimeric Cu/Zn superoxide dismutase (SOD1) mice by transplantation of BM cells 
      derived from mice expressing green fluorescent protein (GFP) in all tissues and 
      from Thy1-YFP mice that express a spectral variant of GFP (yellow fluorescent 
      protein) in neurons only. In the recipient cerebral cortex, we observed rare GFP+ 
      and YFP+ neurons, which were probably generated by cell fusion, as demonstrated 
      by fluorescence in situ hybridization (FISH) analysis, suggesting that this 
      phenomenon is not limited to Purkinje cells. GFP-positive microglial cells were 
      extensively present in both the brain and spinal cord of the affected animals. 
      Completely differentiated and immature GFP+ myofibres were also present in the 
      heart and skeletal muscles of SOD1 mice, confirming that BM cells can participate 
      in striated muscle tissue regeneration. Moreover, wild-type BM chimeric SOD1 mice 
      showed a significantly delayed disease onset and an increased life span, probably 
      due to a positive 'non-neuronal environmental' effect rather than to 
      neuronogenesis. This improvement in SOD1-G93A mouse survival is comparable with 
      that previously obtained using some safer pharmacological agents. BM 
      transplantation-related complications in humans preclude its clinical application 
      for ALS treatment. However, our data suggest that further studies aimed at 
      improving the degree of tissue chimerism by BM-derived cells may provide valuable 
      insights into strategies to slow ALS progression.
FAU - Corti, Stefania
AU  - Corti S
AD  - Centro Dino Ferrari, Dipartimento di Scienze Neurologiche, Universita degli Studi 
      di Milano, IRCCS Ospedale Maggiore Policlinico, Milano, Italy.
FAU - Locatelli, Federica
AU  - Locatelli F
FAU - Donadoni, Chiara
AU  - Donadoni C
FAU - Guglieri, Michela
AU  - Guglieri M
FAU - Papadimitriou, Dimitra
AU  - Papadimitriou D
FAU - Strazzer, Sandra
AU  - Strazzer S
FAU - Del Bo, Roberto
AU  - Del Bo R
FAU - Comi, Giacomo P
AU  - Comi GP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20041006
PL  - England
TA  - Brain
JT  - Brain : a journal of neurology
JID - 0372537
RN  - EC 1.15.1.1 (SOD1 G93A protein)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
MH  - Amyotrophic Lateral Sclerosis/genetics/pathology/*therapy
MH  - Animals
MH  - *Bone Marrow Transplantation
MH  - Cell Differentiation
MH  - Cerebral Cortex/pathology
MH  - In Situ Hybridization, Fluorescence
MH  - Mice
MH  - Mice, Transgenic
MH  - Muscle, Skeletal/pathology
MH  - Myocardium/pathology
MH  - Neurons/pathology
MH  - Phenotype
MH  - Spinal Cord/pathology
MH  - Superoxide Dismutase/*genetics
MH  - Survival Analysis
MH  - Transplantation Chimera
EDAT- 2004/10/08 09:00
MHDA- 2005/01/19 09:00
CRDT- 2004/10/08 09:00
PHST- 2004/10/08 09:00 [pubmed]
PHST- 2005/01/19 09:00 [medline]
PHST- 2004/10/08 09:00 [entrez]
AID - awh273 [pii]
AID - 10.1093/brain/awh273 [doi]
PST - ppublish
SO  - Brain. 2004 Nov;127(Pt 11):2518-32. doi: 10.1093/brain/awh273. Epub 2004 Oct 6.