scholarly journals Generation of Patient-Specific Induced Neuronal Cells Using a Direct Reprogramming Strategy

2014 ◽  
Vol 23 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Pu Wang ◽  
Helen L. Zhang ◽  
Weiguang Li ◽  
Hongying Sha ◽  
Chengshi Xu ◽  
...  
2015 ◽  
Vol 1615 ◽  
pp. 51-60 ◽  
Author(s):  
Penglai Zhao ◽  
Tongming Zhu ◽  
Xiaocheng Lu ◽  
Jianhong Zhu ◽  
Lixin Li

e-Neuroforum ◽  
2013 ◽  
Vol 19 (2) ◽  
Author(s):  
Marisa Karow ◽  
Benedikt Berninger

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.


e-Neuroforum ◽  
2013 ◽  
Vol 19 (2) ◽  
Author(s):  
M. Karow ◽  
B. Berninger

AbstractCellular reprogramming has shed new light on the plasticity of terminally differentiated cells and unearthed novel strategies for cell-based therapies to treat neurological disor­ders. With accumulating knowledge of the programs underlying the genesis of the dis­tinct neural cell types, particularly the iden­tification of crucial 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 three dif­ferent paradigms: (1) direct conversion of central nervous system (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 a strong im­pulse to attempt direct reprogramming in si­tu for future brain repair.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. SCI-40-SCI-40
Author(s):  
George Q. Daley

Abstract Abstract SCI-40 Pluripotent stem cells can be isolated from embryos (embryonic stem cells; ES cells) or generated by direct reprogramming of somatic cells (induced pluripotent stem cells; iPS cells). Both types can be differentiated into a multitude of cell lineages to serve disease research and cell replacement therapies. Additionally, genetically matched pluripotent stem cells generated via nuclear transfer (ntES cells), parthenogenesis (pES cells), or direct reprogramming (iPS cells) are a possible source of histocompatible cells and tissues for transplantation. We have used customized ntES cells to repair genetic immunodeficiency in mice (Rideout et al., Cell 2002); however, generation of ES cells by nuclear transfer remains inefficient, and to date has not been achieved with human cells. We have also generated ES cells with defined histocompatibility loci by direct parthenogenetic activation of the unfertilized oocyte (Kim et al., Science 2007). Compared to ES cell lines from fertilized embryos, pES cells display comparable in vitro hematopoietic activity, but appear compromised in repopulating hematopoiesis in irradiated adult mouse recipients. We are currently comparing the performance of ntES, pES, and iPS cells in murine models of thalassemia. We have generated human iPS cells by direct reprogramming of human somatic cells with OCT4, SOX2, MYC, and KLF4 (Park et al., Nature 2008), and have generated disease-specific iPS cells from patients with a number of hematologic conditions (Park et al., Cell 2008; Agarwal et al., submitted). Applications of disease-specific cells for investigating the mechanisms of reprogramming and for probing aspects of human bone marrow disorders will be discussed. Disclosures Daley: iPierian: Consultancy, Equity Ownership; Epizyme: Consultancy; Solasia: Consultancy; MPM Capital: Consultancy.


2021 ◽  
Vol 13 ◽  
Author(s):  
Fabin Han ◽  
Yanming Liu ◽  
Jin Huang ◽  
Xiaoping Zhang ◽  
Chuanfei Wei

Parkinson’s disease is mainly caused by specific degeneration of dopaminergic neurons (DA neurons) in the substantia nigra of the middle brain. Over the past two decades, transplantation of neural stem cells (NSCs) from fetal brain-derived neural stem cells (fNSCs), human embryonic stem cells (hESCs), and induced pluripotent stem cells (iPSCs) has been shown to improve the symptoms of motor dysfunction in Parkinson’s disease (PD) animal models and PD patients significantly. However, there are ethical concerns with fNSCs and hESCs and there is an issue of rejection by the immune system, and the iPSCs may involve tumorigenicity caused by the integration of the transgenes. Recent studies have shown that somatic fibroblasts can be directly reprogrammed to NSCs, neurons, and specific dopamine neurons. Directly induced neurons (iN) or induced DA neurons (iDANs) from somatic fibroblasts have several advantages over iPSC cells. The neurons produced by direct transdifferentiation do not pass through a pluripotent state. Therefore, direct reprogramming can generate patient-specific cells, and it can overcome the safety problems of rejection by the immune system and teratoma formation related to hESCs and iPSCs. However, there are some critical issues such as the low efficiency of direct reprogramming, biological functions, and risks from the directly converted neurons, which hinder their clinical applications. Here, the recent progress in methods, mechanisms, and future challenges of directly reprogramming somatic fibroblasts into neurons or dopamine neurons were summarized to speed up the clinical translation of these directly converted neural cells to treat PD and other neurodegenerative diseases.


2012 ◽  
Vol 90 (3) ◽  
pp. 317-325 ◽  
Author(s):  
Stefano Pietronave ◽  
Maria Prat

Direct reprogramming of somatic cells into pluripotent cells is an emerging technology for creating patient-specific cells, and potentially opens new scenarios in medical and pharmacological fields. From the discovery of Shinya Yamanaka, who first obtained pluripotent cells from fibroblasts by retrovirus-derived ectopic expression of defined embryonic transcription factors, new methods have been developed to generate safe induced pluripotent stem (iPS) cells without genomic manipulations. This review will focus on the recent advances in iPS technology and their application in pharmacology and medicine.


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