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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2009.1
- 수록면
- 487 - 500 (14page)
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초록· 키워드
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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
(SOD1G93A) 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.
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