Long-Term Survival of Human Central Nervous System Progenitor Cells Transplanted into a Rat Model of Parkinson's Disease

Svendsen, Clive N.; Caldwell, Maeve A.; Shen, Jinkun; Borg, Melanie G. Ter; Rosser, Anne Elizabeth; Tyers, Pam; Karmiol, Soverin; Dunnett, Stephen B.

doi:10.1006/exnr.1997.6634

Cited by 419 publications

(261 citation statements)

References 39 publications

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“…The significant amelioration of hypoactivity in the present HB1.F3 cell-transplanted rats compared with vehicle-infused lesioned rats parallels our previous study demonstrating similar attenuation of abnormal spontaneous locomotor activity in 6-OHDAlesioned animals that received vitamin D3 treatment (Wang et al, 2001). Improvement in drug-induced rotations are observed after transplantation of human or mouse embryonic stem (ES) cells Ben-Hur et al, 2004;Yoshizaki et al, 2004), genetically modified cells (Kang et al, 1993;Leff et al, 1998;Chen et al, 2003), or NSCs or neural progenitor/precursor cells (Svendsen et al, 1997;Armstrong et al, 2002;Sun et al, 2003;Rafuse et al, 2005;Richardson et al, 2005;Harrower et al, 2006). Cell transplantation of rat embryonic VM cells at 2 weeks after 6-OHDA lesion did not attenuate the forelimb akinesia using the cylinder test (Dowd and Dunnett, 2004).…”

Section: Hb1f3 Cell Grafts Attenuate Parkinsonian Motor Symptomssupporting

confidence: 89%

Transplantation of Human Neural Stem Cells Exerts Neuroprotection in a Rat Model of Parkinson's Disease

Yasuhara¹,

Matsukawa²,

Hara³

et al. 2006

J. Neurosci.

260

200

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Section: Hb1f3 Cell Grafts Attenuate Parkinsonian Motor Symptomssupporting

confidence: 89%

Transplantation of Human Neural Stem Cells Exerts Neuroprotection in a Rat Model of Parkinson's Disease

Yasuhara¹,

Matsukawa²,

Hara³

et al. 2006

J. Neurosci.

260

200

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“…We have previously shown that it takes over 20 weeks for GFAP positive astrocytes to develop from hNPC following transplantation into the 6-OHDA lesioned striatum (26), and so perhaps longer time periods are required for full maturation.…”

Section: Discussionmentioning

confidence: 99%

Lesion-Induced Increase in Survival and Migration of Human Neural Progenitor Cells Releasing GDNF

et al. 2008

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The use of human neural progenitor cells (hNPC) has been proposed to provide neuronal replacement or astrocytes delivering growth factors for brain disorders such as Parkinson's and Huntington's disease. Success in such studies likely requires migration from the site of transplantation and integration into host tissue in the face of ongoing damage. In the current study, hNPC modified to release glial cell line derived neurotrophic factor (hNPC GDNF ) were transplanted into either intact or lesioned animals. GDNF release itself had no effect on the survival, migration or differentiation of the cells. The most robust migration and survival was found using a direct lesion of striatum (Huntington's model) with indirect lesions of the dopamine system (Parkinson's model) or intact animals showing successively less migration and survival. No lesion affected differentiation patterns. We conclude that the type of brain injury dictates migration and integration of hNPC which has important consequences when considering transplantation of these cells as a therapy for neurodegenerative diseases.

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“…20,21 Furthermore, a number of reports have shown that hNPC can differentiate into both astrocytes and neurons following transplantation into the nervous system. 18,20,[22][23][24][25] We have previously shown that non-modified hNPC can lead to functional restoration in a model of Huntington's disease, potentially through neuroprotective effects on dying striatal neurons. 21 However, naïve hNPC alone do not have any significant functional effects in models of PD.…”

Section: Introductionmentioning

confidence: 99%

Human neural progenitors deliver glial cell line-derived neurotrophic factor to parkinsonian rodents and aged primates

et al. 2005

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Glial cell line-derived neurotrophic factor (GDNF) has been shown to increase the survival and functioning of dopamine neurons in a variety of animal models and some recent human trials. However, delivery of any protein to the brain remains a challenge due to the blood/brain barrier. Here we show that human neural progenitor cells (hNPC) can be genetically modified to release glycosylated GDNF in vitro under an inducible promoter system. hNPC-GDNF were transplanted into the striatum of rats 10 days following a partial lesion of the dopamine system. At 2 weeks following transplantation, the cells had migrated within the striatum and were releasing physiologically relevant levels of GDNF. This was sufficient to increase host dopamine neuron survival and fiber outgrowth. At 5 weeks following grafting there was a strong trend towards functional improvement in transplanted animals and at 8 weeks the cells had migrated to fill most of the striatum and continued to release GDNF with transport to the substantia nigra. These cells could also survive and release GDNF 3 months following transplantation into the aged monkey brain. No tumors were found in any animal. hNPC can be genetically modified, and thereby represent a safe and powerful option for delivering growth factors to specific targets within the central nervous system for diseases such as Parkinson's.

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Long-Term Survival of Human Central Nervous System Progenitor Cells Transplanted into a Rat Model of Parkinson's Disease

Cited by 419 publications

References 39 publications

Transplantation of Human Neural Stem Cells Exerts Neuroprotection in a Rat Model of Parkinson's Disease

Transplantation of Human Neural Stem Cells Exerts Neuroprotection in a Rat Model of Parkinson's Disease

Lesion-Induced Increase in Survival and Migration of Human Neural Progenitor Cells Releasing GDNF

Human neural progenitors deliver glial cell line-derived neurotrophic factor to parkinsonian rodents and aged primates

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