ABSTRACT
There is longstanding experimental and clinical evidence that supports the idea that replacement of dopaminergic [DAergic] neurons can ameliorate functional disabilities of Parkinson's disease [PD]. The purpose of the present study is to examine the efficacy of transplantation of rat bone marrow stromal cell [BMSCs]-derived tyrosine hydroxylase-positive [TH[+]] cells induced by deprenyl into 6-hydroxydopamine [6-OHDA]-lesioned rat models, using behavioral tests and immunohistochemical evaluations. In this experimental study, undifferentiated BrdU-labeled BM-SCs were incubated in serum-free medium that contained 10[-8] M deprenyl for 24 hours. Afterwards, BMSCs were cultured for 48 hours in alpha-minimal essential medium [alpha-MEM] supplemented with 10% FBS, then differentiated into Th[+] neurons. We randomly divided 24 hemiparkinsonian rats as follows: group 1 [control] received only medium, while groups 2 and 3 were injected with 2x10[5] BMSCs and deprenyl-treated cells in 4 microl medium. Injections were made into the injured strata of the rats. Rotational behavior in response to apomorphine was tested before transplantation and at 2, 4, and 6 weeks post-graft. Animals were then sacrificed, and the brains were extracted for immunohistochemical and electron microscopic studies. Apomorphine-induced rotation analysis indicated that animals with grafted cells in groups 2 and 3 exhibited significantly less rotational behavior than those in the control group at 2, 4, and 6 weeks after transplantation. Immunohistochemical analysis demonstrated that BrdU-labeled cells expressed specific neuronal markers, such as NF 200 and TH, at the implantation site. The presence of TH[+] cells in conjunction with the reduction in rotation might show the capacity of grafted cells to release dopamine. Ultrastructural analysis revealed the presence of immature neurons and astrocyte-like cells at the graft site. Th[+] neurons induced by deprenyl can be considered as a cell source for PD autograft therapy?