An immortalized rat ventral mesencephalic cell line, RTC4, is protective in a rodent model of stroke.
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.
Harvey
B K
BK
Molecular Neuropsychiatry Research Branch, National Institute on Drug Abuse, National Institutes of Health (NIH), Baltimore, MD 21224, USA.
Chen
G J
GJ
Schoen
C J
CJ
Lee
C T
CT
Howard
D B
DB
Dillon-Carter
O
O
Coggiano
M
M
Freed
W J
WJ
Wang
Y
Y
Hoffer
B J
BJ
Sanchez
J F
JF
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*
D006133:Growth Substances; D010982:Platelet-Derived Growth Factor
Brain Res Mol Brain Res. 2003 May 12;113(1-2):44-51
12750005
J Neurosci. 2003 Aug 27;23(21):7958-65
12944527
Exp Neurol. 2003 Sep;183(1):47-55
12957487
Gene Ther. 2003 Dec;10(26):2105-11
14625564
Cell Transplant. 2004;13(3):319-27
15191169
Kobe J Med Sci. 2004 Jan;50(1-2):21-30
15342968
Proc Natl Acad Sci U S A. 1978 May;75(5):2473-7
209467
Mol Cell Biol. 1986 Apr;6(4):1172-8
3023875
Cell. 1987 Jan 30;48(2):321-30
3026642
J Virol. 1992 Mar;66(3):1289-93
1310750
Exp Neurol. 1993 Dec;124(2):368-71
8287932
Exp Neurol. 1993 Dec;124(2):401-12
7904571
Cell Transplant. 1993 Mar-Apr;2(2):151-62
7908247
Brain Res. 1994 Apr 18;643(1-2):162-72
8032912
Brain Res. 2001 May 11;900(2):268-76
11334807
J Cereb Blood Flow Metab. 1999 Dec;19(12):1329-35
10598937
Cancer Lett. 2003 Mar 20;192(1):97-107
12637158
Exp Neurol. 2002 Jun;175(2):318-37
12061863
Exp Neurol. 1994 Aug;128(2):191-201
8076662
J Virol. 1998 Mar;72(3):2224-32
9499080
Metab Brain Dis. 1997 Dec;12(4):271-80
9475500
Cell Tissue Res. 1998 Feb;291(2):175-89
9426306
J Cereb Blood Flow Metab. 1997 Oct;17(10):1097-106
9346435
J Cereb Blood Flow Metab. 1997 May;17(5):500-6
9183287
J Neurosci. 1997 Jun 1;17(11):4341-8
9151750
J Mol Neurosci. 2005;27(2):245-60
16186635
J Neurosurg. 2005 Jul;103(1):38-45
16121971
Brain Res. 1999 Sep 18;842(1):211-4
10526112
Stroke. 1998 Jul;29(7):1417-22
9660398
Brain Res. 1998 Feb 16;784(1-2):250-5
9518639
Neurosci Res. 1997 Dec;29(4):335-43
9527625
Stroke. 1997 Mar;28(3):564-73
9056612