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.
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.
Jingzhong
Zhang
Z
Beijing Institute for Neuroscience Beijing Center for Neural Regeneration and Repairing Capital University of Medical Sciences Beijing, P.R.C.
Hui
Yang
Y
Deyi
Duan
D
Chunli
Duan
D
Chunli
Zhao
Z
Xiaohong
Sun
S
Jinlu
Zhang
Z
Qunyuan
Xu
X
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*
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine