PNAS, December 23, 2003, vol. 100, no. 26,
15983-15988
Published online before print December
10, 2003, 10.1073/pnas.2237050100
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Migration and differentiation of neural precursor cells
can be directed by microglia Johan Aarum, Kristian Sandberg ,
Samantha L. Budd Haeberlein
and Mats A. A. Persson Karolinska Institutet, Department of Medicine and Center for
Molecular Medicine, Karolinska Hospital, 171 76 Stockholm, Sweden [J.A.,
M.A.A.P.]; Astrazeneca
R&D, Novum, S-141 86 Huddinge, Sweden [K.S., S.L.B.H.].
To
whom correspondence should be addressed. E-mail: mats.persson@cmm.ki.se.
[M.A.A.P.].
Communicated by Tomas Hökfelt, Karolinska Institutet, Stockholm, Sweden,
October 30, 2003 (received for review October 10, 2003)
Recent reports have supported the existence of neural stem cells in
the adult mammalian CNS.
Important features of such cells are
self-renewal and multipotency, i.e., they can give rise to neurons,
astrocytes, and oligodendrocytes and thus in principle replace lost
cells in the CNS.
Observations in several animal models of CNS
diseases have shown that by unknown mechanisms endogenous as well as
exogenous precursor cells preferentially migrate to damaged areas.
Microglia are immunoreactive cells of nonneural lineage resident in
the CNS.
After injury to the CNS, microglia are rapidly activated and
found concentrated at the sites of injury.
In the present article we
show, in two different assays, that soluble factors released from
mouse microglial cells direct the migration of neural CNS precursor
cells.
We also provide evidence that microglia have the capacity to
influence the differentiation of both adult and embryonic neural
precursor cells toward a neuronal phenotype.
Given that an invariant
feature of pathological processes in CNS is the activation of
microglia, these results indicate an important and unique role for
microglia in directing the replacement of damaged or lost cells in
the CNS.
Copyright
© 2003 by the National Academy of Sciences
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