One year survival and significant reversal of motor deficits in parkinsonian rats transplanted with hESC derived dopaminergic neurons

Ravindran, Geeta; Ramnath, Rohit; Rao, Harinarayana S.; Viswanathan, Chandra

doi:10.1016/j.bbrc.2008.06.022

Cited by 39 publications

(28 citation statements)

References 23 publications

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“…Cho et al [2008] also established a procedure in which spherical neural masses (SNMs), which are mostly composed of NPs, could be expanded for a long time (at least 120 days) and be coaxed with high efficiency into DA neurons within only 2 weeks. Similar approaches of expanding NPs were also shown in other reports [Geeta et al, 2008].…”

Section: Provision Of Large Amount Of Da Neurons Within a Short Periosupporting

confidence: 71%

Human ES and iPS cells as cell sources for the treatment of Parkinson's disease: Current state and problems

Hwang

Kim

2009

J of Cellular Biochemistry

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Cell therapy using human embryonic stem cells (hESCs) is a promising therapeutic option for Parkinson's disease (PD), an incurable neurodegenerative disease. A prerequisite for clinical application of hESCs for PD is an efficient and strict differentiation of hESCs into midbrain dopamine (mDA) neuron-like cells, which would be directly translated into high effectiveness of the therapy with minimum risk of undesirable side effects. Due to fruitful efforts from many laboratories, a variety of strategies for improving efficiency of dopaminergic differentiation from hESCs have been developed, mostly by optimizing culture conditions, genetic modification, and modulating intracellular signaling pathways. The rapid advances in the fields of dopaminergic differentiation of hESCs, prevention of tumor formation, and establishment of safe human induced pluripotent stem cells (hiPSCs) would open the door to highly effective, tumor-free, and immune rejection-free cell therapy for PD in the near future.

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Section: Provision Of Large Amount Of Da Neurons Within a Short Periosupporting

confidence: 71%

Human ES and iPS cells as cell sources for the treatment of Parkinson's disease: Current state and problems

Hwang

Kim

2009

J of Cellular Biochemistry

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“…However, their degree of maturation seems to be incomplete (although enhanced to some extent by Bcl-X L ) because compensation of apomorphine-induced rotation, which requires normalization of DA receptor expression in target striatal GABA-ergic neurons, did not occur. Behavioral recovery was not complete at the time point studied (2 months), consistent with the well known fact that even fresh fetal tissue requires longer periods (3-6 months) in vivo to generate fully functional DAn (60). Therefore, future studies will be focused on determining the therapeutic effect of hVM1 cells at longer time points (up to 12 months) and on elucidating whether improved maturation occurs over sev- A-E, gene expression.…”

Section: Discussionmentioning

confidence: 96%

In Vitro and in Vivo Enhanced Generation of Human A9 Dopamine Neurons from Neural Stem Cells by Bcl-XL

Courtois

Castillo

Seiz

et al. 2010

Journal of Biological Chemistry

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Parkinson disease (PD)2 motor symptoms arise from the progressive degeneration of dopaminergic neurons (DAn). Experimental therapies, based on the cell replacement of the lost substantia nigra pars compacta (SNpc) DAn using human ventral mesencephalic (VM) fetal tissue provided proof of principle of a therapeutic effect of the transplants on a long term basis (1). However, in addition to ethical problems related to fetal tissue procurement, practical limitations were found, like the need for large amounts of VM tissue and the elevated cell death rate of the transplanted cells (2).As an alternative, human neural stem cells (hNSCs) derived from the developing and adult central nervous system were initially used, but they were inefficient for DAn generation (3). Another stem cell source, the embryonic stem cells, required long and difficult differentiation protocols as well as neuronal and DAn progenitor selection to obtain high amounts of DAn (4, 5). Previous transplantation studies established that the generation of functional SNpc DAn in vivo was highly dependent on the regional tissue origin, the VM being the optimal region (6), and that only DAn with SNpc properties (meaning adequate patterning, transcription factor, and differentiated protein profile) were able to reinervate the striatum and induce a therapeutic effect (7). Therefore, human fetal VM-derived cell strains were established (8, 9), but their use was hindered by a limited and unstable DA differentiation potential (10) (as it was previously described for rodent and human VM neurospheres (11, 12)) and DA-related oxidative stress (13).To the human cell lines of VM origin previously reported (8, 14), we have recently contributed a new immortalized human fetal VM NSC line (hVM1), which shows a great potential for the generation of SNpc DAn in vitro (15). In the present work, we have aimed at increasing our understanding of key factors involved in phenotypical stability, DAn generation, and functional maturation both in vitro and in vivo.

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“…Neurons were not detected in the present experiment. It is important to highlight at this point that human neurons mature very slowly, even when fresh VM tissue is used (over half a year) [31][32][33]. In fact in other studies using hVM cells we have only observed immature neuronal morphologies [5].…”

Section: Long Term Mri Analysismentioning

confidence: 99%

Optimization of the magnetic labeling of human neural stem cells and MRI visualization in the hemiparkinsonian rat brain

Ramos-Gómez¹,

Seiz²,

Martínez‐Serrano³

2016

Nano Online

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Background: Magnetic resonance imaging is the ideal modality for non-invasive in vivo cell tracking allowing for longitudinal studies over time. Cells labeled with superparamagnetic iron oxide nanoparticles have been shown to induce sufficient contrast for in vivo magnetic resonance imaging enabling the in vivo analysis of the final location of the transplanted cells. For magnetic nanoparticles to be useful, a high internalization efficiency of the particles is required without compromising cell function, as well as validation of the magnetic nanoparticles behaviour inside the cells. Results: In this work, we report the development, optimization and validation of an efficient procedure to label human neural stem cells with commercial nanoparticles in the absence of transfection agents. Magnetic nanoparticles used here do not affect cell viability, cell morphology, cell differentiation or cell cycle dynamics. Moreover, human neural stem cells progeny labeled with magnetic nanoparticles are easily and non-invasively detected long time after transplantation in a rat model of Parkinson's disease (up to 5 months post-grafting) by magnetic resonance imaging. Conclusions: These findings support the use of commercial MNPs to track cells for short-and mid-term periods after transplantation for studies of brain cell replacement therapy. Nevertheless, long-term MR images should be interpreted with caution due to the possibility that some MNPs may be expelled from the transplanted cells and internalized by host microglial cells.

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One year survival and significant reversal of motor deficits in parkinsonian rats transplanted with hESC derived dopaminergic neurons

Cited by 39 publications

References 23 publications

Human ES and iPS cells as cell sources for the treatment of Parkinson's disease: Current state and problems

Human ES and iPS cells as cell sources for the treatment of Parkinson's disease: Current state and problems

In Vitro and in Vivo Enhanced Generation of Human A9 Dopamine Neurons from Neural Stem Cells by Bcl-XL

Optimization of the magnetic labeling of human neural stem cells and MRI visualization in the hemiparkinsonian rat brain

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