PMID- 12832537
OWN - NLM
STAT- MEDLINE
DCOM- 20030805
LR  - 20220408
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 23
IP  - 12
DP  - 2003 Jun 15
TI  - Human embryonic germ cell derivatives facilitate motor recovery of rats with 
      diffuse motor neuron injury.
PG  - 5131-40
AB  - We have investigated the potential of human pluripotent cells to restore function 
      in rats paralyzed with a virus-induced motor neuronopathy. Cells derived from 
      embryonic germ cells, termed embryoid body-derived (EBD) cells, introduced into 
      the CSF were distributed extensively over the rostrocaudal length of the spinal 
      cord and migrated into the spinal cord parenchyma in paralyzed, but not 
      uninjured, animals. Some of the transplanted human cells expressed the neuroglial 
      progenitor marker nestin, whereas others expressed immunohistochemical markers 
      characteristic of astrocytes or mature neurons. Rare transplanted cells developed 
      immunoreactivity to choline acetyltransferase (ChAT) and sent axons into the 
      sciatic nerve as detected by retrograde labeling. Paralyzed animals transplanted 
      with EBD cells partially recovered motor function 12 and 24 weeks after 
      transplantation, whereas control animals remained paralyzed. Semi-quantitative 
      analysis revealed that the efficiency of neuronal differentiation and extension 
      of neurites could not account for the functional recovery. Rather, transplanted 
      EBD cells protected host neurons from death and facilitated reafferentation of 
      motor neuron cell bodies. In vitro, EBD cells secrete transforming growth 
      factor-alpha (TGF-alpha) and brain-derived neurotrophic factor (BDNF). 
      Neutralizing antibodies to TGF-alpha and to BDNF abrogated the ability of 
      EBD-conditioned media to sustain motor neuron survival in culture, whereas 
      neutralizing antibodies to BDNF eliminated the axonal outgrowth from spinal 
      organotypics observed with direct coculture of EBD cells. We conclude that cells 
      derived from human pluripotent stem cells have the capacity to restore neurologic 
      function in animals with diffuse motor neuron disease via enhancement of host 
      neuron survival and function.
FAU - Kerr, Douglas A
AU  - Kerr DA
AD  - Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland 21287, USA. dkerr@jhmi.edu
FAU - Llado, Jeronia
AU  - Llado J
FAU - Shamblott, Michael J
AU  - Shamblott MJ
FAU - Maragakis, Nicholas J
AU  - Maragakis NJ
FAU - Irani, David N
AU  - Irani DN
FAU - Crawford, Thomas O
AU  - Crawford TO
FAU - Krishnan, Chitra
AU  - Krishnan C
FAU - Dike, Sonny
AU  - Dike S
FAU - Gearhart, John D
AU  - Gearhart JD
FAU - Rothstein, Jeffrey D
AU  - Rothstein JD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Intermediate Filament Proteins)
RN  - 0 (NES protein, human)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nes protein, rat)
RN  - 0 (Nestin)
RN  - 0 (Transforming Growth Factor alpha)
SB  - IM
MH  - Alphavirus Infections/complications/virology
MH  - Animals
MH  - Antigens, Differentiation/biosynthesis
MH  - Astrocytes/cytology/metabolism
MH  - Brain-Derived Neurotrophic Factor/biosynthesis
MH  - Cell Survival
MH  - Encephalitis, Viral/complications/virology
MH  - Germ Cells/cytology/metabolism/*transplantation
MH  - Graft Survival
MH  - Humans
MH  - Intermediate Filament Proteins/biosynthesis
MH  - Motor Activity
MH  - Motor Neuron Disease/physiopathology/*therapy/virology
MH  - *Nerve Tissue Proteins
MH  - Nestin
MH  - Neurons/cytology/metabolism
MH  - Pluripotent Stem Cells/cytology/metabolism/*transplantation
MH  - Rats
MH  - Rats, Inbred Lew
MH  - *Recovery of Function
MH  - Sindbis Virus/pathogenicity
MH  - *Stem Cell Transplantation
MH  - Transforming Growth Factor alpha/biosynthesis
MH  - Transplantation, Heterologous
MH  - Treatment Outcome
PMC - PMC6741166
EDAT- 2003/07/02 05:00
MHDA- 2003/08/06 05:00
PMCR- 2003/12/15
CRDT- 2003/07/02 05:00
PHST- 2003/07/02 05:00 [pubmed]
PHST- 2003/08/06 05:00 [medline]
PHST- 2003/07/02 05:00 [entrez]
PHST- 2003/12/15 00:00 [pmc-release]
AID - 23/12/5131 [pii]
AID - 10.1523/JNEUROSCI.23-12-05131.2003 [doi]
PST - ppublish
SO  - J Neurosci. 2003 Jun 15;23(12):5131-40. doi: 10.1523/JNEUROSCI.23-12-05131.2003.