scholarly journals Direct Conversion of Mouse Fibroblasts into Neural Stem Cells by Chemical Cocktail Requires Stepwise Activation of Growth Factors and Nup210

Cell Reports ◽  
2018 ◽  
Vol 24 (5) ◽  
pp. 1355-1362.e3 ◽  
Author(s):  
Yuewen Tang ◽  
Shumin Xiong ◽  
Pei Yu ◽  
Feng Liu ◽  
Lin Cheng
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Neural Stem Cells ◽  
Direct Conversion ◽  
Mouse Fibroblasts

Direct conversion of mouse fibroblasts into induced neural stem cells

2014 ◽  
Vol 9 (4) ◽  
pp. 871-881 ◽  
Author(s):  
Sung Min Kim ◽  
Hannah Flaßkamp ◽  
Andreas Hermann ◽  
Marcos Jesús Araúzo-Bravo ◽  
Seung Chan Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Direct Conversion ◽  
Mouse Fibroblasts ◽  
Induced Neural Stem Cells

scholarly journals Generation of Integration-free Induced Neural Stem Cells from Mouse Fibroblasts

2016 ◽  
Vol 291 (27) ◽  
pp. 14199-14212 ◽  
Author(s):  
Sung Min Kim ◽  
Jong-Wan Kim ◽  
Tae Hwan Kwak ◽  
Sang Woong Park ◽  
Kee-Pyo Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Mouse Fibroblasts ◽  
Induced Neural Stem Cells

scholarly journals Direct Reprogramming of Mouse Fibroblasts to Neural Stem Cells by Small Molecules

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Yan-Chuang Han ◽  
Yoon Lim ◽  
Michael D. Duffieldl ◽  
Hua Li ◽  
Jia Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Neural Stem Cells ◽  
Small Molecules ◽  
Clinical Medicine ◽  
Viral Vector ◽  
Expression Patterns ◽  
Tumor Formation ◽  
Patient Specific ◽  
Mouse Fibroblasts

Although it is possible to generate neural stem cells (NSC) from somatic cells by reprogramming technologies with transcription factors, clinical utilization of patient-specific NSC for the treatment of human diseases remains elusive. The risk hurdles are associated with viral transduction vectors induced mutagenesis, tumor formation from undifferentiated stem cells, and transcription factors-induced genomic instability. Here we describe a viral vector-free and more efficient method to induce mouse fibroblasts into NSC using small molecules. The small molecule-induced neural stem (SMINS) cells closely resemble NSC in morphology, gene expression patterns, self-renewal, excitability, and multipotency. Furthermore, the SMINS cells are able to differentiate into astrocytes, functional neurons, and oligodendrocytesin vitroandin vivo. Thus, we have established a novel way to efficiently induce neural stem cells (iNSC) from fibroblasts using only small molecules without altering the genome. Such chemical induction removes the risks associated with current techniques such as the use of viral vectors or the induction of oncogenic factors. This technique may, therefore, enable NSC to be utilized in various applications within clinical medicine.

Die Kunst des Neuronenschmiedens: Direkte Reprogrammierung somatischer Zellen in induzierte neuronale Zellen

e-Neuroforum ◽  
2013 ◽  
Vol 19 (2) ◽  
Author(s):  
Marisa Karow ◽  
Benedikt Berninger
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Neuronal Cells ◽  
Somatic Cells ◽  
Cell Types ◽  
Direct Conversion ◽  
Cellular Reprogramming ◽  
Direct Reprogramming ◽  
Brain Pericytes

AbstractThe art of forging neurons: direct reprogramming of somatic cells into induced neu­ronal cells.Cellular reprogramming has shed new light on the plasticity of terminally differentiated cells and discloses novel strategies for cell-based therapies for neurological disorders. With accumulating knowledge of the programs underlying the genesis of the distinct neural cell types, especially with the identification of relevant transcription factors and microRNAs, reprogramming of somatic cells of different origins into induced neuronal cells or neural stem cells has been successfully achieved. Starting with the general con­cept of reprogramming we discuss here three different paradigms: 1) direct conversion of CNS-foreign cells such as skin fibroblasts into induced neuronal cells or neural stem cells; 2) transdifferentiation of CNS resident cells such as astrocytes and brain pericytes into induced neuronal cells; 3) reprogramming of one neuronal subtype into another. The latter has already been successfully achieved in vivo during early brain develop­ment, providing strong impulse for the attempt to succeed in direct reprogramming in situ for future brain repair.

Temporal changes in the response of SVZ neural stem cells to intraventricular administration of growth factors

2016 ◽  
Vol 1636 ◽  
pp. 118-129 ◽  
Author(s):  
Takashi Ochi ◽  
Hirofumi Nakatomi ◽  
Akihiro Ito ◽  
Hideaki Imai ◽  
Shigeo Okabe ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Neural Stem Cells ◽  
Temporal Changes ◽  
Intraventricular Administration

290 EFFECT OF EXOGENOUS Oct4 PROTEIN ON DIRECT CONVERSION OF HUMAN FIBROBLASTS INTO NEURAL STEM CELLS

2013 ◽  
Vol 25 (1) ◽  
pp. 292
Author(s):  
J. H. Kang ◽  
S. M. Park ◽  
S. Y. Heo ◽  
H. Shim
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Human Fibroblasts ◽  
Autologous Transplantation ◽  
Direct Conversion ◽  
Protein Transduction ◽  
Oct4 Protein ◽  
Reprogramming Factors ◽  
Cell Stem Cell

The generation of neural stem cells (NSC) from somatic cells may provide unlimited source of neuronal cells for autologous transplantation to patients of neurological disorders. Recently, direct conversion of fibroblasts into NSC by epigenetic reprogramming has been reported (Han et al. 2012 Cell Stem Cell 10, 465–472; Thier et al. 2012 Cell Stem Cell 10, 473–479; Ring et al. 2012 Cell Stem Cell 11, 100–109). These reprogrammed cells are referred to as induced neural stem cells (iNSC) and they share the characteristics of NSC in their morphology, molecular marker expressions, and capacity to differentiate into neurons, astrocytes, and oligodendrocytes. One of the procedures to convert fibroblasts into iNSC is restriction of Oct4 activity to the initial phase of reprogramming, while Sox2, Klf4, and c-Myc are constitutively expressed. In the present study, we examined the effect of Oct4 in reprogramming of human fibroblasts into iNSC. Oct4 protein was modified by the addition of poly-arginine protein transduction domain to easily penetrate into the cell membrane. We transduced Oct4 protein, in contrast to the previous reports where the Oct4 gene was virally introduced. First, human fibroblasts were transfected by retroviral vectors carrying the genes encoding Sox2, Klf4, and c-Myc. Then, transfected cells were cultured in ReNcell NSC maintenance medium containing Oct4 protein. After 4 days, Oct4 protein was removed from the medium. With Oct4 protein transduction, 21 flat colonies were formed from 4 × 105 fibroblasts. These colonies were picked and passaged for subculture and later became iNSC. However, in the absence of Oct4 protein, no colonies were obtained from the same number of fibroblasts that were initially plated. Approximately 40 days after transduction of reprogramming factors, cluster of iNSC were obtained. These cells expressed molecular markers of human NSC, including Nestin, Sox2, Pax6, and Blbp. Moreover, these iNSC could differentiate into neurons, astrocytes, and oligodendrocytes in vitro. Results of the present study demonstrate that transduction of exogenous Oct4 protein may be essential to the direct conversion of human fibroblasts into iNSC using a combination of reprogramming factors Sox2, Klf4, and c-Myc.

scholarly journals Differentiation of Neural Stem Cells Into Cells of Oligodendroglial Lineage

2007 ◽  
Vol 50 (1) ◽  
pp. 35-41
Author(s):  
Jaroslav Mokrý ◽  
Jana Karbanová ◽  
Dana Čížková ◽  
Jan Pazour ◽  
Stanislav Filip ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Cell Differentiation ◽  
Neural Stem Cells ◽  
Developmental Stages ◽  
Developmental Studies ◽  
Differentiation Markers ◽  
Lineage Differentiation ◽  
Massive Cell Death

We described three different conditions that induce differentiation of dissociated neural stem cells derived from mouse embryonic CNS. In the first set of experiments, where the cell differentiation was triggered by cell adhesion, removal of growth factors and serum-supplemented medium, only sporadic neuronal and astroglial cells survived longer than two weeks and the latter formed a monolayer. When differentiation was induced in serum-free medium supplemented with retinoic acid, rapid and massive cell death occurred. A prolonged survival was observed in cultivation medium supplemented with serum and growth factors EGF plus FGF-2. One third of the cells did not express cell differentiation markers and were responsible for an increase in cell numbers. The remaining cells differentiated and formed the astrocytic monolayer on which occasional neuronal cells grew. One third of the differentiated phenotypes were represented by cells of oligodendroglial lineage. Differentiation of oligodendroglial cells occurred in a stepwise mechanism because the culture contained all successive developmental stages, including oligodendrocyte progenitors, preoligodendrocytes and immature and mature oligodendrocytes. Maturing oligodendrocytes displayed immunocytochemical and morphological features characteristic of cells that undergo physiological development. The cultivation conditions that supported growth and differentiation of neural stem cells were optimal for in vitro developmental studies and the production of oligodendroglial cells.

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