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T155g-immortalized kidney cells produce growth factors and reduce sequelae of cerebral ischemia
- Source :
- Cell Transplantation, Vol 11 (2002)
- Publication Year :
- 2002
-
Abstract
- Fetal rat kidney cells produce high levels of glial-derived neurotrophic factor (GDNF) and exert neuroprotective effects when transplanted into the brain in animal models of Parkinson's disease and stroke. The purpose of the present experiment was to produce kidney cell lines that secrete GDNF. Genes encoding two truncated N-terminal fragments of SV40 large T antigen, T155g and T155c, which does not code for small t antigen, were used. T155g was transduced into E17 cultured fetal Sprague-Dawley rat kidney cortex cells using a plasmid vector, and T155c was transduced with a plasmid and a retroviral vector. Sixteen clones were isolated from cultures transfected with the T155g-expressing plasmid. No cell lines were obtained with T155c. Four clones produced GDNF at physiological concentrations ranging from 55 to 93 pg/ml of medium. These four clones were transplanted into the ischemic core or penumbra of rats that had undergone middle cerebral artery occlusion (MCAO). Three of the four clones reduced the volume of infarction and the behavioral abnormalities normally resulting from MCAO. Blocking experiments with antibodies to GDNF and platelet-derived growth factor (PDGF) suggested that these growth factors contributed only minimally to the reduction in infarct volume and behavioral abnormality. These cell lines may be useful for intracerebral transplantation in animal models of brain injury, stroke, or Parkinson's disease.
- Subjects :
- 0301 basic medicine
Male
Kidney Cortex
Cell Transplantation
medicine.medical_treatment
Antigens, Polyomavirus Transforming
Biomedical Engineering
Ischemia
lcsh:Medicine
Motor Activity
Transfection
Antibodies
Viral vector
Cell Line
Rats, Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Neurotrophic factors
Fetal Tissue Transplantation
Glial cell line-derived neurotrophic factor
medicine
Animals
Humans
Glial Cell Line-Derived Neurotrophic Factor
Nerve Growth Factors
Growth Substances
Cell Line, Transformed
Cerebral Cortex
Transplantation
Kidney
biology
Behavior, Animal
Growth factor
lcsh:R
Infarction, Middle Cerebral Artery
Cell Biology
medicine.disease
Molecular biology
Rats
Stroke
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Neuroprotective Agents
Cell culture
Anesthesia
biology.protein
030217 neurology & neurosurgery
Platelet-derived growth factor receptor
Subjects
Details
- ISSN :
- 09636897
- Volume :
- 11
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Cell transplantation
- Accession number :
- edsair.doi.dedup.....a531683ca366db389534ec85da434863