title: An immortalized rat ventral mesencephalic cell line, RTC4, is protective in a rodent model of stroke.
abstract: One therapeutic approach to stroke is the transplantation of cells capable of trophic support, reinnervation, and/or regeneration. Previously, we have described the use of novel truncated isoforms of SV40 large T antigen to generate unique cell lines from several primary rodent tissue types. Here we describe the generation of two cell lines, RTC3 and RTC4, derived from primary mesencephalic tissue using a fragment of mutant T antigen, T155c (cDNA) expressed from the RSV promoter. Both lines expressed the glial markers vimentin and S100beta, but not the neuronal markers NeuN, MAP2, or beta-III-tubulin. A screen for secreted trophic factors revealed substantially elevated levels of platelet-derived growth factor (PDGF) in RTC4, but not RTC3 cells. When transplanted into rat cortex, RTC4 cells survived for at least 22 days and expressed PDGF. Because PDGF has been reported to reduce ischemic injury, we examined the protective functions of RTC4 cells in an animal model of stroke. RTC4 or RTC3 cells, or vehicle, were injected into rat cortex 15-20 min prior to a 60-min middle cerebral artery ligation. Forty-eight hours later, animals were sacrificed and the stroke volume was assessed by triphenyl-tetrazolium chloride (TTC) staining. Compared to vehicle or RTC3 cells, transplanted RTC4 cells significantly reduced stroke volume. Overall, we generated a cell line with glial properties that produces PDGF and reduces ischemic injury in a rat model of stroke.
authors: Molecular Neuropsychiatry Research Branch, National Institute on Drug Abuse, National Institutes of Health (NIH), Baltimore, MD 21224, USA.
authors: B K
authors: BK
authors: Harvey
authors: G J
authors: GJ
authors: Chen
authors: C J
authors: CJ
authors: Schoen
authors: C T
authors: CT
authors: Lee
authors: D B
authors: DB
authors: Howard
authors: O
authors: O
authors: Dillon-Carter
authors: M
authors: M
authors: Coggiano
authors: W J
authors: WJ
authors: Freed
authors: Y
authors: Y
authors: Wang
authors: B J
authors: BJ
authors: Hoffer
authors: J F
authors: JF
authors: Sanchez
mesh_terms: D000818:Animals; D016923:Cell Death; D002461:Cell Line, Transformed; D002470:Cell Survival; D002544:Cerebral Infarction / Q000139:chemically induced / Q000517:prevention & control; D004195:Disease Models, Animal; D006133:Growth Substances / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000166:cytology* / Q000637:transplantation; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000517:prevention & control*
chemical_list: D006133:Growth Substances; D010982:Platelet-Derived Growth Factor
references: Brain Res Mol Brain Res. 2003 May 12;113(1-2):44-51
references: 12750005
references: J Neurosci. 2003 Aug 27;23(21):7958-65
references: 12944527
references: Exp Neurol. 2003 Sep;183(1):47-55
references: 12957487
references: Gene Ther. 2003 Dec;10(26):2105-11
references: 14625564
references: Cell Transplant. 2004;13(3):319-27
references: 15191169
references: Kobe J Med Sci. 2004 Jan;50(1-2):21-30
references: 15342968
references: Proc Natl Acad Sci U S A. 1978 May;75(5):2473-7
references: 209467
references: Mol Cell Biol. 1986 Apr;6(4):1172-8
references: 3023875
references: Cell. 1987 Jan 30;48(2):321-30
references: 3026642
references: J Virol. 1992 Mar;66(3):1289-93
references: 1310750
references: Exp Neurol. 1993 Dec;124(2):368-71
references: 8287932
references: Exp Neurol. 1993 Dec;124(2):401-12
references: 7904571
references: Cell Transplant. 1993 Mar-Apr;2(2):151-62
references: 7908247
references: Brain Res. 1994 Apr 18;643(1-2):162-72
references: 8032912
references: Brain Res. 2001 May 11;900(2):268-76
references: 11334807
references: J Cereb Blood Flow Metab. 1999 Dec;19(12):1329-35
references: 10598937
references: Cancer Lett. 2003 Mar 20;192(1):97-107
references: 12637158
references: Exp Neurol. 2002 Jun;175(2):318-37
references: 12061863
references: Exp Neurol. 1994 Aug;128(2):191-201
references: 8076662
references: J Virol. 1998 Mar;72(3):2224-32
references: 9499080
references: Metab Brain Dis. 1997 Dec;12(4):271-80
references: 9475500
references: Cell Tissue Res. 1998 Feb;291(2):175-89
references: 9426306
references: J Cereb Blood Flow Metab. 1997 Oct;17(10):1097-106
references: 9346435
references: J Cereb Blood Flow Metab. 1997 May;17(5):500-6
references: 9183287
references: J Neurosci. 1997 Jun 1;17(11):4341-8
references: 9151750
references: J Mol Neurosci. 2005;27(2):245-60
references: 16186635
references: J Neurosurg. 2005 Jul;103(1):38-45
references: 16121971
references: Brain Res. 1999 Sep 18;842(1):211-4
references: 10526112
references: Stroke. 1998 Jul;29(7):1417-22
references: 9660398
references: Brain Res. 1998 Feb 16;784(1-2):250-5
references: 9518639
references: Neurosci Res. 1997 Dec;29(4):335-43
references: 9527625
references: Stroke. 1997 Mar;28(3):564-73
references: 9056612