scholarly journals Chemical conversion of human fibroblasts into neuronal cells: dawn of future clinical trials

2015 ◽  
Vol 56 (3) ◽  
pp. 165-165 ◽  
Author(s):  
Shinya Toyokuni
Keyword(s):  
Clinical Trials ◽  
Human Fibroblasts ◽  
Neuronal Cells ◽  
Chemical Conversion

scholarly journals Chemical Conversion of Human Fibroblasts into Functional Schwann Cells

2014 ◽  
Vol 3 (4) ◽  
pp. 539-547 ◽  
Author(s):  
Eva C. Thoma ◽  
Claudia Merkl ◽  
Tobias Heckel ◽  
Rachel Haab ◽  
Frederic Knoflach ◽  
...  
Keyword(s):  
Schwann Cells ◽  
Human Fibroblasts ◽  
Chemical Conversion

scholarly journals Highly efficient direct conversion of human monocytes into neuronal cells using a small molecule combination

2019 ◽  
Author(s):  
Itaru Ninomiya ◽  
Masato Kanazawa ◽  
Akihide Koyama ◽  
Masahiro Hatakeyama ◽  
Osamu Onodera
Keyword(s):  
Small Molecules ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Human Fibroblasts ◽  
Neuronal Cells ◽  
Neuronal Cell ◽  
Direct Conversion ◽  
Dermal Fibroblasts ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes

SummaryPrevious studies reported that human fibroblasts and astrocytes were successfully converted into neuronal cells by small molecules without introducing ectopic transgenes. Induced neuronal cells—reprogrammed directly from dermal fibroblasts or brain astrocytes—were obtained from some donors; however, the clinical applications of this approach would be limited because it requires an invasive biopsy to harvest enough cells for derivation. Here, we report that adult human peripheral blood monocytes may be directly converted into neuron-like cells using only a combination of small molecules without transgene integration. This method enables neuronal cell generation from TUJ1-positive cells after 3 days of induction (at over 80% conversion efficacy). These cells presented neuronal morphologies and markers, suggesting that terminally differentiated human cells may be efficiently transdifferentiated into a distantly related lineage. Overall, our study provides a strategy to develop neuronal cells directly from human adult peripheral blood monocytes using a generate transgene-free, chemical-only approach.

scholarly journals Direct Conversion of Normal and Alzheimer’s Disease Human Fibroblasts into Neuronal Cells by Small Molecules

2015 ◽  
Vol 17 (2) ◽  
pp. 204-212 ◽  
Author(s):  
Wenxiang Hu ◽  
Binlong Qiu ◽  
Wuqiang Guan ◽  
Qinying Wang ◽  
Min Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Small Molecules ◽  
Human Fibroblasts ◽  
Neuronal Cells ◽  
Direct Conversion

scholarly journals Enhanced conversion of induced neuronal cells (iN cells) from human fibroblasts: Utility in uncovering cellular deficits in mental illness-associated chromosomal abnormalities

2015 ◽  
Vol 101 ◽  
pp. 57-61 ◽  
Author(s):  
Eleonora Passeri ◽  
Ashley M. Wilson ◽  
Amedeo Primerano ◽  
Mari A. Kondo ◽  
Srona Sengupta ◽  
...  
Keyword(s):  
Mental Illness ◽  
Chromosomal Abnormalities ◽  
Human Fibroblasts ◽  
Neuronal Cells ◽  
In Cells

scholarly journals Toward allele-specific targeting therapy and pharmacodynamic marker for spinocerebellar ataxia type 3

2020 ◽  
Vol 12 (566) ◽  
pp. eabb7086 ◽  
Author(s):  
Mercedes Prudencio ◽  
Hector Garcia-Moreno ◽  
Karen R. Jansen-West ◽  
Rana Hanna AL-Shaikh ◽  
Tania F. Gendron ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Gene Silencing ◽  
Spinocerebellar Ataxia ◽  
Biological Fluids ◽  
Human Fibroblasts ◽  
Cag Repeat ◽  
Spinocerebellar Ataxia Type ◽  
Spinocerebellar Ataxia Type 3 ◽  
Targeting Therapy ◽  
Type 3

Spinocerebellar ataxia type 3 (SCA3), caused by a CAG repeat expansion in the ataxin-3 gene (ATXN3), is characterized by neuronal polyglutamine (polyQ) ATXN3 protein aggregates. Although there is no cure for SCA3, gene-silencing approaches to reduce toxic polyQ ATXN3 showed promise in preclinical models. However, a major limitation in translating putative treatments for this rare disease to the clinic is the lack of pharmacodynamic markers for use in clinical trials. Here, we developed an immunoassay that readily detects polyQ ATXN3 proteins in human biological fluids and discriminates patients with SCA3 from healthy controls and individuals with other ataxias. We show that polyQ ATXN3 serves as a marker of target engagement in human fibroblasts, which may bode well for its use in clinical trials. Last, we identified a single-nucleotide polymorphism that strongly associates with the expanded allele, thus providing an exciting drug target to abrogate detrimental events initiated by mutant ATXN3. Gene-silencing strategies for several repeat diseases are well under way, and our results are expected to improve clinical trial preparedness for SCA3 therapies.

scholarly journals Chemical conversion of human lung fibroblasts into neuronal cells

2018 ◽  
Author(s):  
Xiao‑Yu Wan ◽  
Li‑Yun Xu ◽  
Bing Li ◽  
Qiu‑Hong Sun ◽  
Qiu‑Liang Ji ◽  
...  
Keyword(s):  
Human Lung ◽  
Neuronal Cells ◽  
Chemical Conversion ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts
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