The effects of transforming growth factor-beta2 on dopaminergic graft survival.
Dopaminergic cell transplantation is a promising therapeutic approach for the treatment of Parkinson's disease, the potential of which is limited due to poor survival and low dopamine content within engrafted tissue. In this study, the ability of transforming growth factor-beta2 (TGF-beta2) to influence transplant survival was evaluated. Cell suspensions containing fetal rat ventral mesencephalon (VM) cells were incubated prior to surgery with vehicle (DPBS), varying concentrations of TGF-beta2 (5-1000 ng/ml), or a pan-specific antibody against TGF-beta (1D11, 100 ng/ml). VM cell suspensions (200,000 cells) were unilaterally implanted into the striatum of adult Sprague-Dawley rats (n = 5-11 animals/group). Following a 3-week survival period, small but viable VM grafts containing tyrosine hydroxylase-positive (TH+) neurons and fibers were present in all animals. Addition of TGF-beta2 resulted in a steep, bell-shaped dose-response curve with a significant effect on TH+/dopamine cell survival. At 50 ng/ml TGF-beta2, the number of surviving dopamine neurons was increased twofold compared with controls. Addition of TGF-beta2 or 1D11 did not significantly influence graft volume. Further studies, possibly in combination with other neurotrophic factors, need to be performed to obtain a greater understanding of the effects of TGF-beta on dopamine neurons and fetal VM cell engraftment.
Macauley
Shannon L
SL
Genzyme Corporation, Framingham, MA 01701, USA.
Horsch
Alexander D
AD
Oterdoom
Marinus
M
Zheng
Ming H
MH
Stewart
Gregory R
GR
D000818:Animals; D000906:Antibodies / Q000737:chemistry; D016380:Brain Tissue Transplantation / Q000379:methods*; D002470:Cell Survival; D017690:Cell Transplantation / Q000379:methods*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016332:Fetal Tissue Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008636:Mesencephalon / Q000166:cytology; D009474:Neurons / Q000166:cytology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000737:chemistry; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053781:Transforming Growth Factor beta2; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000906:Antibodies; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine