A simple method for large‐scale generation of dopamine neurons from human embryonic stem cells

Morizane, Asuka; Darsalia, Vladimer; Guloglu, M. Oktar; Hjalt, Tord; Carta, Manolo; Li, Jiayi; Brundin, Patrik

doi:10.1002/jnr.22515

Cited by 21 publications

(16 citation statements)

References 44 publications

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“…Presence of TH and NURR1 positive cells in our culture confirms that some of the cells are dopaminergic in nature. It has been shown that human ES-derived neuronal progenitors could be differentiated into neurons, exhibiting midbrain DA phenotype, expressing Aldh1a, PTX3, NURR1 and LMX1a by repeated passaging in the presence of basic fibroblast growth factor and medium conditioned with PA6 stromal cells [28]. Studies have shown that DA neurons acquiring SNpc specificity requires PITX3 to be induced [29].…”

Section: Discussionmentioning

confidence: 99%

Engraftment of Mouse Embryonic Stem Cells Differentiated by Default Leads to Neuroprotection, Behaviour Revival and Astrogliosis in Parkinsonian Rats

et al. 2013

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We report here protection against rotenone-induced behavioural dysfunction, striatal dopamine depletion and nigral neuronal loss, following intra-striatal transplantation of neurons differentiated from murine embryonic stem cells (mES). mES maintained in serum free medium exhibited increase in neuronal, and decrease in stem cell markers by 7th and 10th days as revealed by RT-PCR and immunoblot analyses. Tyrosine hydroxylase, NURR1, PITX3, LMX1b and c-RET mRNA showed a significant higher expression in differentiated cells than in mES. Dopamine level was increased by 3-fold on 10th day as compared to 7 days differentiated cells. Severity of rotenone-induced striatal dopamine loss was attenuated, and amphetamine-induced unilateral rotations were significantly reduced in animals transplanted with 7 days differentiated cells, but not in animals that received undifferentiated ES transplant. However, the ratio of contralateral to ipsilateral swings in elevated body swing test was significantly reduced in both the transplanted groups, as compared to control. Striatal grafts exhibited the presence of tyrosine hydroxylase positive cells, and the percentage of dopaminergic neurons in the substantia nigra was also found to be higher in the ipsilateral side of 7 days and mES grafted animals. Increased expression of CD11b and IBA-1, suggested a significant contribution of these microglia-derived factors in controlling the limited survival of the grafted cells. Astrocytosis in the grafted striatum, and significant increase in the levels of glial cell line derived neurotrophic factor may have contributed to the recovery observed in the hemiparkinsonian rats following transplantation.

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Section: Discussionmentioning

confidence: 99%

Engraftment of Mouse Embryonic Stem Cells Differentiated by Default Leads to Neuroprotection, Behaviour Revival and Astrogliosis in Parkinsonian Rats

et al. 2013

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“…Alternatively, ES cells offer sources for large-scale production of neurons which acquire a midbrain DA phenotype. 40, 41 Grafting both ES- and MSC-derived DA neurons into rat PD models results in functional recovery. 42, 43 The ability to produce patient-specific DA neurons has recently been demonstrated using iPS cells.…”

Section: Cellular Therapy For Neurodegenerative Diseasesmentioning

confidence: 99%

Stem cell technology for neurodegenerative diseases

Lunn

Sakowski

Hur

et al. 2011

Annals of Neurology

233

170

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Over the past 20 years, stem cell technologies have become an increasingly attractive option to investigate and treat neurodegenerative diseases. In the current review, we discuss the process of extending basic stem cell research into translational therapies for patients suffering from neurodegenerative diseases. We begin with a discussion on the burden of these diseases on society, emphasizing the need for increased attention towards advancing stem cell therapies. We then explain the various types of stem cells utilized in neurodegenerative disease research, and outline important issues to consider in the transition of stem cell therapy from bench to bedside. Finally, we detail the current progress regarding the applications of stem cell therapies to specific neurodegenerative diseases, focusing on Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis and spinal muscular atrophy. With a greater understanding of the capacity of stem cell technologies, there is growing public hope that stem cell therapies will continue to progress into realistic and efficacious treatments for neurodegenerative diseases.

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“…This factor has been reported to help in maintaining the specific properties of different progenitor cell types. For example, hESC-derived neuronal progenitors were found to retain their full capacity to generate dopamine neurons after repeated passaging in the presence of FGF2 (Morizane et al, 2010). FGF2 has been shown to increase the lifespan and potential for differentiation of mesenchymal stem cells from the bone marrow (Bianchi et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Tooth Engineering: Searching for Dental Mesenchymal Cells Sources

Keller¹,

Kuchler‐Bopp²,

Mendoza³

et al. 2011

Front. Physio.

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The implantation of cultured re-associations between embryonic dental mesenchymal cells and epithelial cells from mouse molars at embryonic day 14 (ED14) allowed making full teeth with crown, root, periodontal ligament fibers, and bone. Although representing valuable tools to set up methodologies embryonic cells are not easily available. This work thus aimed to replace the embryonic cells by dental mesenchymal cell lines or cultured expanded embryonic cells, and to test their ability to mediate tooth development in vitro when re-associated with a competent dental epithelium. Histology, immunostaining and RT-PCR allowed getting complementary sets of results. Two different immortalized cell lines from ED18 dental mesenchyme failed in mediating tooth formation. The potentialities of embryonic dental mesenchymal cells decreased from ED14 to ED16 and were lost at ED18. This is likely related to a change in the mesenchymal cell phenotype and/or populations during development. Attempts to cultivate ED14 or ED16 embryonic dental mesenchymal cells prior to re-association led to the loss of their ability to support tooth development. This was accompanied by a down-regulation of Fgf3 transcription. Supplementation of the culture medium with FGF2 allowed restoring Fgf3 expression, but not the ability of mesenchymal cells to engage in tooth formation. Altogether, these observations suggest that a competent cell population exists in the dental mesenchyme at ED14, progressively decreases during development, and cannot as such be maintained in vitro. This study evidenced the need for specific conditions to maintain the ability of dental mesenchymal cells to initiate whole tooth formation, when re-associated with an odontogenic epithelium. Efforts to improve the culture conditions will have to be combined with attempts to characterize the competent cells within the dental mesenchyme.

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A simple method for large‐scale generation of dopamine neurons from human embryonic stem cells

Cited by 21 publications

References 44 publications

Engraftment of Mouse Embryonic Stem Cells Differentiated by Default Leads to Neuroprotection, Behaviour Revival and Astrogliosis in Parkinsonian Rats

Engraftment of Mouse Embryonic Stem Cells Differentiated by Default Leads to Neuroprotection, Behaviour Revival and Astrogliosis in Parkinsonian Rats

Stem cell technology for neurodegenerative diseases

Tooth Engineering: Searching for Dental Mesenchymal Cells Sources

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