Cellular Alchemy: Converting Adult Human Stem Cells into Nerve Cells

Guest Speaker:
Dr Darius Widera (School of Pharmacy, University of Reading)
Host:
Dr Wee Kiat Ong (UoRM)
Subject Area:
Pharmacy
Activity:
Seminar
Date & Time:
Mon, 22. February 2016, 12:30 h - 14:00 h
Venue:
N3.23, University of Reading Malaysia - EduCity@Iskandar​

Abstract ​
Restoring the tissue integrity after acute injuries and compensation for the progressive loss of cells during degenerative disorders using current pharmacological treatment strategies is limited and remains challenging. Here, stem cell-based cell replacement therapies represent a promising therapeutic alternative. Although the use of pluripotent stem cells is a possible therapeutic option, the clinical application of foetal tissue, human embryonic stem cells and induced pluripotent stem cells is limited due to solid ethical and practical considerations (e.g. limited availability or tumorigenicity). In contrast, adult neural crest-derived stem cells (NCSCs) can be readily isolated and possess an extraordinarily high developmental potential surpassed only by pluripotent cells. We previously reported isolation of NCSCs from various human craniofacial tissues including the periodontal ligament, hard palate and nasal turbinates. Revealing their multipotent character, NCSCs were able to generate mesodermal cells including adipocytes, chondrocytes and osteoblasts in addition to ectodermal neuron-like cells and glia. Moreover, NCSCs can be phenotypically switched towards forebrain-like neurons, as shown by a characteristic morphology and expression of mature neuronal markers including Synaptophysin, vGlut2 and GAT-1. Functionality of NCSC-derived neurons was demonstrated by their ability to recycle synaptic vesicles and repeated calcium spiking after KCl-stimulation. Transplantation into murine organotypic hippocampal slice cultures resulted in neuronal differentiation and integration of NCSCs into pre-existing neuronal networks. In addition, using dual-SMAD inhibition and sequential treatment with SHH and FGF-8 we successfully differentiated NCSCs into TH-positive, dopaminergic-like neurons in vitro. Transplantation of undifferentiated and NCSCs pre-differentiated towards midbrain neurons into a unilaterally lesioned 6-OHDA rat model resulted in improved motor functions in both groups. In conclusion, our findings emphasize that adult human NCSCs have the potential for treating a broad spectrum of degenerative disorders and acute lesions affecting more than one cell type.

01 Biography​
Dr Widera is currently a Lecturer in Stem Cell Biology and Regenerative Medicine at the University of Reading, United Kingdom. His lab is mainly interested in neural crest-derived stem cell populations, which are promising candidates for the development of autologous stem cell-based therapies. He further works on the influence of injury and inflammation on stem cells and somatic cells (injury-induced cellular reprogramming) and develops novel approaches for clinical grade 3D-cultivation of human stem cells. He graduated in Biochemistry (Witten/Herdecke University, Germany) and received his PhD in Neurobiochemistry from the Witten/Herdecke University in Germany. Since 2013 he served as a Principal Investigator and Adjunct Professor at the Department of Cell Biology, University of Bielefeld (Germany). In February 2015 he was appointed Assistant Professor/ Lecturer in Stem Cell Biology and Regenerative Medicine at the University of Reading (United Kingdom), where his lab is currently based. Since May 2015 he also serves as a Visiting Professor at the Stavropol State Medical University (Russian Federation). In December 2015 he also joined the Expert Panel for the DEBRA International charity. He has published over 40 PubMed-listed publications in addition to several book chapters and has presented his research outcomes at numerous international conferences in the UK, Germany, USA, Russia, Brazil and China. In addition, he serves as an Associate Editor for the journal Frontiers in Stem Cell Research and acts as an ad-hoc peer reviewer for funding bodies (including DEBRA International, German Academic Exchange Service (DAAD, Germany), National Medical Research Council (NMRC, Singapore), The Daphne Jackson Trust (United Kingdom), Neurological Foundation Of New Zealand (New Zealand), the Anniversary Fund of the Austrian National Bank for Basic Science (Austria), University of Luxembourg (Luxembourg) and renowned journals including Biomaterials, Stroke, Stem Cells and Development, and European Cells and Materials.
  • Admission to this seminar is free and open to academics, students and external parties who work in a related field. ​

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