TY - JOUR
T1 - Co-grafts of fetal ventral mesencephalon and fibroblasts expressing Sonic hedgehog
T2 - Effect on survival and function of dopamine grafts
AU - Yurek, D. M.
AU - Fletcher-Turner, A.
AU - Moore, J.
AU - Chai, L.
PY - 2001
Y1 - 2001
N2 - Fibroblasts derived from the Rat2 parental cell line were genetically modified to express the cell-associated form of Sonic hedgehog (Shh) and then co-grafted along with E14 fetal ventral mesencephalon (VM) tissue into the denervated striatum of F344 rats; fetal VM grafts alone or co-grafts using the nonexpressing Rat2 fibroblasts served as controls. Seven weeks after grafting, co-grafts of fetal VM and fibroblasts expressing Shh (Rat2/Shh) contained significantly more tyrosine hydroxylase-positive (TH+) neurons than either the fetal VM grafts or co-grafts of fetal VM plus nonexpressing fibroblasts (Rat2). Despite a significantly higher yield of grafted TH+ neurons in the fetal VM + Rat2/Shh co-grafts than in either of the other two control groups, amphetamine-induced rotational behavior scores were not significantly different between any of the three treatment groups. The number of TH+ neurons in the Rat2 (nonexpressing) co-grafts was significantly lower than the other two treatment groups. The results from this study suggest that fibroblasts expressing Shh may improve the number of co-grafted dopamine neurons, but do not improve the functional capacity of the graft in terms of improving amphetamine-induced rotational behavior.
AB - Fibroblasts derived from the Rat2 parental cell line were genetically modified to express the cell-associated form of Sonic hedgehog (Shh) and then co-grafted along with E14 fetal ventral mesencephalon (VM) tissue into the denervated striatum of F344 rats; fetal VM grafts alone or co-grafts using the nonexpressing Rat2 fibroblasts served as controls. Seven weeks after grafting, co-grafts of fetal VM and fibroblasts expressing Shh (Rat2/Shh) contained significantly more tyrosine hydroxylase-positive (TH+) neurons than either the fetal VM grafts or co-grafts of fetal VM plus nonexpressing fibroblasts (Rat2). Despite a significantly higher yield of grafted TH+ neurons in the fetal VM + Rat2/Shh co-grafts than in either of the other two control groups, amphetamine-induced rotational behavior scores were not significantly different between any of the three treatment groups. The number of TH+ neurons in the Rat2 (nonexpressing) co-grafts was significantly lower than the other two treatment groups. The results from this study suggest that fibroblasts expressing Shh may improve the number of co-grafted dopamine neurons, but do not improve the functional capacity of the graft in terms of improving amphetamine-induced rotational behavior.
KW - Dopamine
KW - Fetal ventral mesencephalon
KW - Genetically modified fibroblasts
KW - Neural transplantation
KW - Parkinson's disease
KW - Rodent
KW - Sonic hedgehog
UR - http://www.scopus.com/inward/record.url?scp=0035696416&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035696416&partnerID=8YFLogxK
U2 - 10.3727/000000001783986305
DO - 10.3727/000000001783986305
M3 - Article
C2 - 11814108
AN - SCOPUS:0035696416
SN - 0963-6897
VL - 10
SP - 665
EP - 671
JO - Cell Transplantation
JF - Cell Transplantation
IS - 8
ER -