An Immortalized Rat Ventral Mesencephalic Cell Line, RTC4, Is Protective in a Rodent Model of Stroke

• Published in: Cell transplantation Vol. 16; no. 5; pp. 483 - 491
• Main Authors: Harvey, B. K., Chen, G. J., Schoen, C. J., Lee, C. T., Howard, D. B., Dillon-Carter, O., Coggiano, M., Freed, W. J., Wang, Y., Hoffer, B. J., Sanchez, J. F.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.01.2007; SAGE Publishing
• Subjects: Animals; Cell Death; Cell Line, Transformed; Cell Survival; Cerebral Infarction - chemically induced; Cerebral Infarction - prevention & control; Disease Models, Animal; Growth Substances - metabolism; Male; Mesencephalon - cytology; Mesencephalon - transplantation; Phenotype; Platelet-Derived Growth Factor - metabolism; Rats; Rats, Sprague-Dawley; Stroke - prevention & control; Platelet-derived growth factor (PDGF); Stroke; Transplantation; Ischemia; Ventral mesencephalon
• ISSN: 0963-6897; 1555-3892
• DOI: 10.3727/000000007783464984

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 S100β, but not the neuronal markers NeuN, MAP2, or β-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.