Transplantation of organ and tissue are common in clinical practices for treating chronic diseases. In case of neurodegeneration in the central nervous system (CNS), organ transplant is not possible and hence, cell therapy is an innovation in clinical practice. Transplantation of progenitor's cells with differentiation properties or differentiated cells is a promising approach in treating neurological diseases such as Alzheimer's type dementia, Parkinson's disease (PD), Huntington's disease (HD), stroke and trauma [1, 2].
Parkinson's disease is one among the common neurodegenerative disorders, caused by the degeneration of nigrostriatal dopamine neurons. Transplantation of cell and tissue has been developed as a clinical approach for treating PD [3-10]. Nevertheless, the treatment is limited to the availability of donor tissue. One of the alternative cell sources for transplantation could be immortalized cell lines . It has been shown that transplantation with conditionally immortalized progenitor's cells could be useful in treating PD [12, 13]. Immortalized cell lines also helps in elucidating the mechanism of cellular differentiation.
There are several ways (Table 1) to immortalize primary neuronal cells namely somatic fusion , v-myc , SV40 large T antigen (LT) [16, 17] and human telomerase . The commonly used vector for immortalization is SV40 LT, which exhibits immortalizing properties without fully transforming the cells . The focus of this review is on the cell lines established from mesencephalic progenitors, as it is shown in vivo that mesencephalic progenitors differentiate into dopaminergic neurons. The article attempts to discuss the mechanism of generating differentiated dopaminergic neurons and their application for transplantation, breaking them down into three divisions: (1) the molecular mechanism of transformation by SV40 LT and discusses the factors involved in immortalization, (2) the influences of genes in differentiation of dopaminergic neurons and the characteristic features of SV40 immortalized neuronal cell lines with respect to dopaminergic differentiation, (3) transplantation studies and the limitation for cell therapy with stem cells in PD patients.
|Immortalizing agent||Cell line||Characteristic features||Transplantation experiments||Reference|
|Somatic fusion [hypoxanthine phosphoribosyltransferase- deficient neuroblastoma cell line (N18TG2)]||E14 mouse rostral mesencephalic tegmentum (MN9D)||Express neurofilament||Choi et al. |
|c-myc||E11 mouse embryonic midbrain (A1)|| |
Express vimentin and nestin, MAP, co-stained for GFAP and NSE
No TH and DAT mRNA expression
Glutamic acid decarboxylase mRNA has been observed
|Colucci-D'Amato et al. |
|c-mycERTAM (c-myc protein fused with a mutated oestrogen receptor)||Human ventral mesencephalic cells 10 week old aborted foetus)||Nestin positive, differentiate TH in vitro||Rodent PD model: Improved behavioural recovery, no TH differentiation in vivo, but increased host TH immunoreactivity||Miljan et al. |
|v-myc||Human ventral mesencephalic cells (10 week old aborted foetus; hVM1)||Express Lmx1A, Lmx1B, Girk2, ADH2, Nurr1, Pitx3, VMAT2 and DAT, βIII-tubulin and TH|| |
Transplantation of hVM1- Bcl-XL in Hemiparkinsonian rats: No tumour formation, integrated into host parenchyma, expresses TH, DAT
Apomorphine-induced rotation was not compensated, while amphetamine-induced rotations were compensated 
|Villa et al. , Tonnesen et al. |
|Human ventral mesencephalic cells (8 week-old aborted foetus; MESC2.10)|| |
Proliferation: Express Nurr1 and GFR α1
Differentiation: Express TH, GFR α1 and c-ret mRNA increased
|Hemiparkinsonian rats: No TH expression, no behavioural recovery in amphetamine-induced motor asymmetry test||Paul et al. |
|Telomerase (hTERT)||Human foetal subventricular zone (hNPC-TERT)|| |
Proliferation: Co-express nestin and GFAP
Differentiation: Express MAP2, O1 and GFAP i.e. differentiate into neurons, oligodendrocyte and astrocytes respectively)
|Spinal injury models: Recovery of motor functions and electrophysiological parameters ||Bai et al. |