Enhanced survival, reinnervation, and functional recovery of intrastriatal dopamine grafts co-transplanted with Schwann cells overexpressing high molecular weight FGF-2 isoforms

Timmer, Marco; Müller-Ostermeyer, Frauke; Kloth, Verena; Winkler, Christian; Grothe, Claudia; Nikkhah, Guido

doi:10.1016/j.expneurol.2004.01.013

Cited by 60 publications

(46 citation statements)

References 72 publications

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“…These and other insults may also decrease the functional capacity of the surviving tyrosine hydroxylase immunorecative (THir) neurons. Treatment of transplanted DA neurons with neurotrophic factors such as BDNF, NT-3, GDNF, aFGF, and bFGF has been shown to increase the number and functional capacity of grafted THir neurons (Giacobini, et al, 1993;Granholm, et al, 1997;Rosenblad, et al, 1996;Timmer, et al, 2004;Yurek, et al, 1996). However, this approach is only able to increase survival rates to approximately 30-35%, still leaving poor survival as a major obstacle preventing transplantation of primary mesencephalic tissue from becoming a viable therapy for PD (Sortwell, 2003 ).…”

Section: Introductionmentioning

confidence: 99%

Increased cell suspension concentration augments the survival rate of grafted tyrosine hydroxylase immunoreactive neurons

Terpstra

Collier

Marchionini

et al. 2007

Journal of Neuroscience Methods

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Section: Introductionmentioning

confidence: 99%

Increased cell suspension concentration augments the survival rate of grafted tyrosine hydroxylase immunoreactive neurons

Terpstra

Collier

Marchionini

et al. 2007

Journal of Neuroscience Methods

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“…In the dopaminergic nigrostriatal system, FGF-2 and three of its respective receptors (FGFR1-FGFR3) are endogenously expressed Timmer et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Fibroblast Growth Factor (FGF)-2 and FGF Receptor 3 Are Required for the Development of the Substantia Nigra, and FGF-2 Plays a Crucial Role for the Rescue of Dopaminergic Neurons after 6-Hydroxydopamine Lesion

Cesnulevicius²,

et al. 2007

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Basic fibroblast growth factor (FGF-2) is involved in the development and maintenance of the nervous system. Exogenous administration of FGF-2 increased dopaminergic (DA) graft survival in different animal models of Parkinson's disease. To study the physiological function of the endogenous FGF-2 system, we analyzed the nigrostriatal system of mice lacking FGF-2, mice overexpressing FGF-2, and FGF-receptor-3 (FGFR3)-deficient mice both after development and after 6-hydroxydopamine lesion. FGFR3-deficient mice (ϩ/Ϫ) displayed a reduced number of DA neurons compared with the respective wild type. Whereas absence of FGF-2 led to significantly increased numbers of DA neurons, enhanced amount of the growth factor in mice overexpressing FGF-2 resulted in less tyrosine hydroxylase expression and a reduced DA cell density. The volumes of the substantia nigra were enlarged in both FGF-2 Ϫ/Ϫ and in FGF-2 transgenic mice, suggesting an important role of FGF-2 for the establishment of the proper number of DA neurons and a normal sized substantia nigra during development. In a second set of experiments, the putative relevance of endogenous FGF-2 after neurotoxin application was investigated regarding the number of rescued DA neurons after partial 6-OHDA lesion. Interestingly, the results after lesion were directly opposed to the results after development: significantly less DA neurons survived in FGF-2 Ϫ/Ϫ mice compared with wild-type mice. Together, the results indicate that FGFR3 is crucially involved in regulating the number of DA neurons. The lack of FGF-2 seems to be (over)compensated during development, but, after lesion, compensation mechanisms fail. The transgenic mice showed that endogenous FGF-2 protects DA neurons from 6-OHDA neurotoxicity.

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“…Fetal VMC has also been co-grafted with a wide variety of other tissues or cells, including peripheral nerve/Schwann cells [45] , immature astrocyte [46] , striatal tissue [47] , Sertoli cells [48] and fetal kidney [49] . Motor function improvements were observed in all these research.…”

Section: Other Cellsmentioning

confidence: 99%

How to improve the survival of the fetal ventral mesencephalic cell transplanted in Parkinson’s disease?

Liu¹,

Huang²

2007

Neurosci. Bull.

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It has been extensively confirmed that fetal ventral mesencephalic cell (VMC) transplantation can ameliorate the symptoms of Parkinson's disease (PD). But there are still several problems to be resolved before the extensive clinical application of this technology. The major limitations are the poor survival of grafted dopamine (DA) neurons and restricted dopaminergic reinnervation of host striatum. Some attempts have been made to solve these problems including use of some trophic factor and co-transplantation with neural/paraneural origins. The purpose of this review is to overview advances of the means improving the survival of grafts and their current limitations.

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Enhanced survival, reinnervation, and functional recovery of intrastriatal dopamine grafts co-transplanted with Schwann cells overexpressing high molecular weight FGF-2 isoforms

Cited by 60 publications

References 72 publications

Increased cell suspension concentration augments the survival rate of grafted tyrosine hydroxylase immunoreactive neurons

Increased cell suspension concentration augments the survival rate of grafted tyrosine hydroxylase immunoreactive neurons

Fibroblast Growth Factor (FGF)-2 and FGF Receptor 3 Are Required for the Development of the Substantia Nigra, and FGF-2 Plays a Crucial Role for the Rescue of Dopaminergic Neurons after 6-Hydroxydopamine Lesion

How to improve the survival of the fetal ventral mesencephalic cell transplanted in Parkinson’s disease?

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