PT  - JOURNAL ARTICLE
AU  - A Martinez-Serrano
AU  - C Lundberg
AU  - P Horellou
AU  - W Fischer
AU  - C Bentlage
AU  - K Campbell
AU  - RD McKay
AU  - J Mallet
AU  - A Bjorklund
TI  - CNS-derived neural progenitor cells for gene transfer of nerve growth factor to the adult rat brain: complete rescue of axotomized cholinergic neurons after transplantation into the septum
AID  - 10.1523/JNEUROSCI.15-08-05668.1995
DP  - 1995 Aug 01
TA  - The Journal of Neuroscience
PG  - 5668--5680
VI  - 15
IP  - 8
4099  - http://www.jneurosci.org/content/15/8/5668.short
4100  - http://www.jneurosci.org/content/15/8/5668.full
SO  - J. Neurosci.1995 Aug 01; 15
AB  - A CNS-derived conditionally immortalized temperature-sensitive neural progenitor (CINP) cell line was used to generate NGF-secreting cells suitable for intracerebral transplantation. The cells were transduced by repeated retroviral infection, using a vector containing the mouse NGF cDNA under the control of the LTR promoter. Subcloning at the permissive temperature (33 degrees C) identified a highly NGF-secreting clone (NGF-CINP), which contained multiple copies of the transgene and released NGF at a rate of 2 ng/hr/10(5) cells in vitro, both at 33 and 37 degrees C, which was approximately 1 order of magnitude higher than what was possible to achieve in the heterogeneously infected cell cultures. After transplantation to the brain, the NGF-CINPs differentiated into cells with a predominant glia-like morphology and migrated for a distance of 1–1.5 mm from the implantation site into the surrounding host tissue, without any signs of overgrowth and tumor formation. Grafts of NGF-CINP cells implanted into the septum of adult rats with complete fimbria-fornix lesion blocked over 90% of the cholinergic cell loss in the medial septum and grafts placed in the intact striatum induced accumulation of low-affinity NGF receptor positive fibers around the implantation site. Expression of the NGF transgene in vivo was demonstrated by RT-PCR at 2 weeks after grafting. It is concluded that the immortalized neural progenitors have a number of advantageous properties that make them highly useful experimental tools for gene transfer to the adult CNS.