Expression of Early Developmental Markers Predicts the Efficiency of Embryonic Stem Cell Differentiation into Midbrain Dopaminergic Neurons

Salti, Ahmad; Nat, Roxana; Neto, Sonya; Puschban, Zoe; Wenning, Gregor K.; Dechant, Georg

doi:10.1089/scd.2012.0238

Cited by 19 publications

(20 citation statements)

References 70 publications

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“…Differentiated cultures yield 5–15% mDA neurons (Salti et al, 2013). When characterizing lines, this low yield seemed to exaggerate phenotypic differences.…”

Section: Resultsmentioning

confidence: 99%

iPSC-Derived Dopamine Neurons Reveal Differences between Monozygotic Twins Discordant for Parkinson’s Disease

et al. 2014

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SUMMARY Parkinson’s disease (PD) has been attributed to a combination of genetic and non-genetic factors. We studied a set of monozygotic twins harboring the heterozygous glucocerebrosidase mutation (GBA N370S) but clinically discordant for PD. We applied induced pluripotent stem (iPS) cell technology for PD disease modeling using the twins’ fibroblasts to evaluate and dissect the genetic and non-genetic contributions. Utilizing fluorescence-activated cell sorting, we obtained a homogenous population of ‘footprint-free’ iPS cell-derived midbrain dopaminergic (mDA) neurons. The mDA neurons from both twins had ~ 50% GBA enzymatic activity, ~ 3-fold elevated α-synuclein protein levels, and a reduced capacity to synthesize and release dopamine. Interestingly, the affected twin’s neurons showed an even lower dopamine level, increased monoamine oxidase B (MAO-B) expression, and impaired intrinsic network activity. Overexpression of wild-type GBA and treatment of MAO-B inhibitors normalized α-synuclein and dopamine levels, suggesting a combination therapy for the affected twin.

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“…Differentiated cultures yield 5–15% mDA neurons (Salti et al, 2013). When characterizing lines, this low yield seemed to exaggerate phenotypic differences.…”

Section: Resultsmentioning

confidence: 99%

iPSC-Derived Dopamine Neurons Reveal Differences between Monozygotic Twins Discordant for Parkinson’s Disease

et al. 2014

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“…Differentiation induction of ES cells by Shh and FGF8 resulted in about 30% TH‐expressing cells, which was three‐fold compared to control (Parmar and Li, ). Heterogeneity of cell populations obtained in vitro is still one of the major challenges in transplantation strategies (Salti et al , ). Therefore, the enrichment of DA neurons to provide a scalable pool for transplantation purposes in PD patients has been a goal of investigators for many years (Perrone‐Capano and Di Porzio, ).…”

Section: Discussionmentioning

confidence: 99%

“…However, the replacement strategies still need further investigation to overcome the major challenges in this field. A large number of studies have focused on the generation of DA neurons from pluripotent cells (Cho et al , ; Gale and Li, ; Salti et al , ). So far, a number of growth factors and cytokines have been applied for in vitro expansion of DA neuron precursor population (Perrone‐Capano and Di Porzio, ).…”

Section: Introductionmentioning

confidence: 99%

Induction of Tyrosine Hydroxylase Gene Expression in Embryonal Carcinoma Stem Cells Using a Natural Tissue‐Specific Inducer

Momendoust

Moshtaghian

Esmaeili

et al. 2019

Developmental Neurobiology

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A large number of studies have focused on the generation of dopaminergic neurons from pluripotent cells. Differentiation of stem cells into distinct cell types is influenced by tissue-specific microenvironment. Since, central nervous system undergoes further development during postnatal life, in the present study neonatal rat brain tissue extract (NRBE) was applied to direct the differentiation of embryonal carcinoma stem cell line, P19 into dopaminergic (DA) phenotypes. Additionally, a neuroprotective drug, deprenyl was used alone or in combination with the extract. Results from morphological, immunofluorescence, and qPCR analyses showed that during a period of one to three weeks, a large percentage of stem cells were differentiated into neural cells. The results also indicated the greater effect of NRBE on the differentiation of the cells into tyrosine hydroxylase-expressing cells. MS analysis of NRBE showed the enrichment of gene ontology terms related to cell differentiation and neurogenesis. Network analysis of the studied genes and some DA markers resulted in the suggestion of potential regulatory candidates such as AVP, ACHE, LHFPL5, and DLK1 genes. In conclusion, NRBE as a natural native inducer was apparently able to simulate the brain microenvironment and support neural differentiation of P19 cells.

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“…This is of particular relevance due to the reported variation in differentiation abilities and efficiencies of various PSC lines. [2][3][4] The relative importance of a range of in vitro and in vivo assessments within the context of a cell standardization framework was investigated. Of the in vivo assessments, ''tumorgenicity'' (score 9.5) and ''immune response'' (score 5.5) were rated as the most important parameters (Fig.…”

Section: ‰ Barriers To Translation Of Pluripotent Stem Cell Therapiesmentioning

confidence: 99%

CASMI TSCC Launch Event, Paris, France, July 2013: An Assessment of the Key Barriers to the Commercialization and Clinical Adoption of Pluripotent Stem Cell Therapies

French

Bure²,

Brindley

2014

Rejuvenation Research

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The high incidence of unmet medical needs in combination with the rising burden of chronic diseases, linked to an increasingly aging population, necessitates new approaches to therapeutic intervention. One potential class of health care innovation that may offer an alternative approach to addressing current shortfalls is stem cell therapies. The CASMI Translational Stem Cell Consortium (CTSCC) was formed to elucidate the key hurdles to the commercialization and clinical adoption of stem cell technologies, with a particular focus on pluripotent stem cell (PSC) technologies. As a global pre-competitive academic-industry consortium, the CTSCC unites thought leaders from a range of sectors and technical specialties in defining and discovering solutions to roadblocks that will impede the field. Targeted toward stakeholder requirements at the delivery end of the translational spectrum, the CTSCC aims to provide mechanisms for multidirectional dialogue and to produce academically rigorous and commercially practicable research outputs to accelerate industry progress. On the 30th and 31st of July, 2013, the CASMI Translational Stem Cell Consortium (CTSCC) held a launch event at the Saint James Club,

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Expression of Early Developmental Markers Predicts the Efficiency of Embryonic Stem Cell Differentiation into Midbrain Dopaminergic Neurons

Cited by 19 publications

References 70 publications

iPSC-Derived Dopamine Neurons Reveal Differences between Monozygotic Twins Discordant for Parkinson’s Disease

iPSC-Derived Dopamine Neurons Reveal Differences between Monozygotic Twins Discordant for Parkinson’s Disease

Induction of Tyrosine Hydroxylase Gene Expression in Embryonal Carcinoma Stem Cells Using a Natural Tissue‐Specific Inducer

CASMI TSCC Launch Event, Paris, France, July 2013: An Assessment of the Key Barriers to the Commercialization and Clinical Adoption of Pluripotent Stem Cell Therapies

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