Abstract
With the help of several inducing factors, somatic cells can be reprogrammed to become induced pluripotent stem cell (iPSCs) lines. The success is in obtaining iPSCs almost identical to embryonic stem cells (ESCs), therefore various approaches have been tested and ultimately several ones have succeeded. The importance of these cells is in how they serve as models to unveil the molecular pathways and mechanisms underlying several human diseases, and also in its potential roles in the development of regenerative medicine. They further aid in the development of regenerative medicine, autologous cell therapy and drug or toxicity screening. Here, we provide a comprehensive overview of the recent development in the field of iPSCs research, specifically for modeling human neurological and neurodegenerative diseases, and its applications in neurotrauma. These are mainly characterized by progressive functional or structural neuronal loss rendering them extremely challenging to manage. Many of these diseases, including Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) have been explored in vitro. The main purpose is to generate patient-specific iPS cell lines from the somatic cells that carry mutations or genetic instabilities for the aim of studying their differentiation potential and behavior. This new technology will pave the way for future development in the field of stem cell research anticipating its use in clinical settings and in regenerative medicine in order to treat various human diseases, including neurological and neurodegenerative diseases.
Highlights
Stem cell research is considered one of the most captivating areas of cell biology mainly due to the unique properties of stem cells and their potential use in cell-based therapies to treat a variety of diseases, including Parkinson’s disease (PD), Alzheimer’s diseases (AD), Diabetes Mellitus (DM), and many others (Correia et al, 2005; Pagliuca et al, 2014; Sproul, 2015)
Treating HD-specific NSCs (HD-NSCs) with SHH, DKK1, BDNF and ROCK inhibitor Y27632 for 8–10 days, with BDNF, cAMP, VPA, and Y27632 for an additional 1-3 days (Chambers et al, 2009) neural differentiation protocol used revealing that the lengths of CAG trinucleotide repeats in the generated neurons is not affected by the differentiation process human iPSCs (hiPSCs), human induced pluripotent stem cells; HD, Huntington’s disease; embryoid bodies (EBs), embryoid body; SHH, sonic hedgehog; DKK1, Dickkopf WNT signaling pathway inhibitor 1; BDNF, brain-derived neurotrophic factor; VPA, valproic acid; HD-NSCs: HD, specific neural stem cells
In a recent work published in 2015, Nieweg et al used human iPSC-derived cortical neurons, differentiated using an EB system similar to that applied by Li et al (2015), to produce a highly reproducible cellular AD model that facilitates the mechanistic analysis of amyloid beta (Aβ)-induced synaptic pathomechanisms and the development of new therapeutic approaches (Nieweg et al, 2015)
Summary
Stem cell research is considered one of the most captivating areas of cell biology mainly due to the unique properties of stem cells and their potential use in cell-based therapies to treat a variety of diseases, including Parkinson’s disease (PD), Alzheimer’s diseases (AD), Diabetes Mellitus (DM), and many others (Correia et al, 2005; Pagliuca et al, 2014; Sproul, 2015). A more recent protocol combined neural stem cells (NSCs) transplantation with a trehalose enriched diet in R6/2 mice and resulted in more improved motor functions, less aggregations in iPSCs for Modeling Human Neurodegenerative Diseases
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