In vitro characterization of human bone marrow mesenchymal stem cell-derived motor neurons induced by epigenetic modifiers

Background: Motor neurons (MNs) are distinct types of cells in the dorso-ventral axis of the spinal cord. These cells are developed in the presence of two main morphogens, including Sonic hedgehog (Shh) and retinoic acid (RA). On the other hand, human bone marrow mesenchymal stem cells (hBM-MSCs) are known as a multipotent type of cells with neural differentiation capacity. In this regard, the aim of this study was to quantitatively evaluate the expression of MN-related genes and the potent epigenetic regulatory genes involved in neurogenesis, including Enhancer of zeste homolog 2 (EZH-2) and P300, during hBM-MSC differentiation into MN-like cells, using RA and Shh. After isolating and inducing the cells with Shh and RA, the results were evaluated using immunocytochemistry and qRT-PCR. Results: Our findings showed that the treated cells could express choline acetyltransferase (ChAT) and insulin gene enhancer binding protein-1 (Islet-1) antigens at the protein level, 2 weeks after induction. Moreover, at the second week after induction, the induced cells expressed MN-related genes (ChAT and ISLET-1) and epigenetic regulatory genes (EZH-2 and P300) at significant levels compared to the control (non-treated BM-MSCs) and to the induced cells at the first week (day 7). In addition, the expression of EZH-2, as a histone-modifying gene, was also significantly upregulated at the first week compared to the control. No significant upregulation was detected in the expression of motor neuron and pancreas homeobox 1 (MNX-1) in the treated groups compared to the control group. Conclusion: We concluded that epigenetic modifiers, P300 and EZH-2, are important mediators for regulating the process of motor neuron differentiation induced by RA and Shh. © 2021, The Author(s)

Correction to: Transplantation of Human Chorion-Derived Cholinergic Progenitor Cells: a Novel Treatment for Neurological Disorders

The original version of this article unfortunately contained mistake in the affiliation. Affiliation 1 should be read as �Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran�. The original article has been corrected. © 2018 Springer Science+Business Media, LLC, part of Springer Natur

Correction to: Transplantation of Human Chorion-Derived Cholinergic Progenitor Cells: a Novel Treatment for Neurological Disorders

The original version of this article unfortunately contained mistake in the affiliation. Affiliation 1 should be read as �Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran�. The original article has been corrected. © 2018 Springer Science+Business Media, LLC, part of Springer Natur

Correction to: Transplantation of Human Chorion-Derived Cholinergic Progenitor Cells: a Novel Treatment for Neurological Disorders (Molecular Neurobiology, (2019), 56, 1, (307-318), 10.1007/s12035-018-0968-1)

The original version of this article unfortunately contained mistake in the affiliation. Affiliation 1 should be read as �Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran�. The original article has been corrected. © 2018, Springer Science+Business Media, LLC, part of Springer Nature

Transplantation of Human Chorion-Derived Cholinergic Progenitor Cells: a Novel Treatment for Neurological Disorders

A neurological disorder is any disorder or abnormality in the nervous system. Among different neurological disorders, Alzheimer�s disease (AD) is recognized as the sixth leading cause of death globally. Considerable research has been conducted to find pioneer treatments for this devastating disorder among which cell therapy has attracted remarkable attentions over the last decade. Up to now, targeted differentiation into specific desirable cell types has remained a major obstacle to clinical application of cell therapy. Also, potential risks including uncontrolled growth of stem cells could be disastrous. In our novel protocol, we used basal forebrain cholinergic progenitor cells (BFCN) derived from human chorion-derived mesenchymal stem cells (hC-MSCs) which made it possible to obtain high-quality population of cholinergic neurons and in vivo in much shorter time period than previous established methods. Remarkably, the transplanted progenitors fully differentiated to cholinergic neurons which in turn integrated in higher cortical networks of host brains, resulting in significant improvement in cognitive assessments. This method may have profound implications in cell therapies for any other neurodegenerative disorders. Figure not available: see fulltext. © 2018, Springer Science+Business Media, LLC, part of Springer Nature

Transplantation of Human Chorion-Derived Cholinergic Progenitor Cells: a Novel Treatment for Neurological Disorders

NoA neurological disorder is any disorder or abnormality in the nervous system. Among different neurological disorders, Alzheimer’s disease (AD) is recognized as the sixth leading cause of death globally. Considerable research has been conducted to find pioneer treatments for this devastating disorder among which cell therapy has attracted remarkable attentions over the last decade. Up to now, targeted differentiation into specific desirable cell types has remained a major obstacle to clinical application of cell therapy. Also, potential risks including uncontrolled growth of stem cells could be disastrous. In our novel protocol, we used basal forebrain cholinergic progenitor cells (BFCN) derived from human chorion-derived mesenchymal stem cells (hC-MSCs) which made it possible to obtain high-quality population of cholinergic neurons and in vivo in much shorter time period than previous established methods. Remarkably, the transplanted progenitors fully differentiated to cholinergic neurons which in turn integrated in higher cortical networks of host brains, resulting in significant improvement in cognitive assessments. This method may have profound implications in cell therapies for any other neurodegenerative disorders.This work was carried outwithin the framework of a collaborative project (Project Grant No. 94-02-30-25922) by the School of Medicine, Iran University of Medical Sciences, (Project Grant No. REP209) council for stem cell sciences and technologies (Presidency of the Islamic Republic of Iran, vice-presidency for science and technology), and Iran National Science Foundation (INSF)