title: Long-term therapeutic effects on parkinsonian rats of intrastriatal co-grafts with genetically engineered fibroblasts expressing tyrosine hydroxylase and glial cell line-derived neurotrophic factor.
abstract: The long-term improvement of intrastriatal co-grafts with genetically engineered fibroblasts expressing tyrosine hydroxylase (TH) and glial cell line-derived neurotrophic factor (GDNF) was investigated in the present study. Two recombinant vectors, pCMV-TH and pCI-neo-GDNF, were transfected respectively into the primary fibroblasts, and their expression was further identified by in situ hybridization and immunocytochemistry. The engineered fibroblasts expressing TH, GDNF, or both were transplanted into the striatum of parkinsonian rats, and the therapeutic effects were observed for 20 weeks. Data revealed that only animals with fibroblasts expressing both TH and GDNF exhibited a stable and significant behavioral and biochemical recovery. Moreover, persistence of both TH and GDNF expression in grafts was demonstrated 20 weeks after transplantation. These results suggest that combined transplantation of fibroblasts expressing TH and GDNF can lead to long-term and remarkable therapeutic effects on parkinsonian rat model.
authors: Beijing Institute for Neuroscience Beijing Center for Neural Regeneration and Repairing Capital University of Medical Sciences Beijing, P.R.C.
authors: Zhang
authors: Z
authors: Jingzhong
authors: Yang
authors: Y
authors: Hui
authors: Duan
authors: D
authors: Deyi
authors: Duan
authors: D
authors: Chunli
authors: Zhao
authors: Z
authors: Chunli
authors: Sun
authors: S
authors: Xiaohong
authors: Zhang
authors: Z
authors: Jinlu
authors: Xu
authors: X
authors: Qunyuan
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000196:embryology / Q000378:metabolism / Q000637:transplantation*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology*; D018014:Gene Transfer Techniques; D005818:Genetic Engineering / Q000379:methods*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D009414:Nerve Growth Factors; D010300:Parkinson Disease / Q000201:enzymology* / Q000378:metabolism / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013995:Time; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine