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The differentiation of PC12 cells into a neuronal-like morphology is improved by both nerve growth factor and Schwann cells

Carol L-Y Zhou-Zheng (1, 2), Yogambha Ramaswamy (2), Hala Zreiqat (2) and R. M. Damian Holsinger (1, 3)

  1. Laboratory of Molecular Neuroscience and Dementia, Brain and Mind Centre, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, New South Wales, Australia

  2. Tissue Engineering & Biomaterials Research Unit, School of Aerospace, Mechanical & Mechatronic Engineering, Faculty of Engineering and Information Technologies, The University of Sydney, New South Wales, Australia

  3. Discipline of Pathology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, New South Wales, Australia

Peripheral nerve injuries (PNIs) involve the interruption in the transmission of information along an axon. There are varying degrees of severity and thus varying effectiveness of treatment. PNIs can result in loss of sensory or effector function. This debilitative and painful condition is estimated to impact 2-3% of all patients worldwide. Schwann cells, the glial cell of the peripheral nervous system (PNS), play several important roles during peripheral nerve regeneration. These include the secretion of trophic factors and other proteins that encourage axonal growth and subsequent remyelination. Axonal growth and remyelination thus become indicators of nerve repair. Current focus in PNI research involves direct implantation of Schwann cells or Schwann cell-like differentiated stem cells, which aim to take advantage of the reparative ability of Schwann cells. PC12 cells, rat pheochromocytoma cells of neural crest origin, are often differentiated into neuron-like cells through a well-documented pathway – treatment with nerve growth factor (NGF). The aim of this study was to examine whether both NGF and Schwann cells would enhance axonal growth, cell viability and myelination of PC12 cells. We observed that the proliferation and differentiation of PC12 cells to form axonal processes were significantly improved in the presence of both NGF and Schwann cells. When PC12 cells were grown in cocultures with Schwann cells and treated with NGF, the morphology of neurites and neurite length were more developed compared to NGF-treated monocultures. Our findings demonstrate a feature of Schwann cells that will aid PNI treatment and the future direction of peripheral nerve regeneration research could be significantly impacted. Although there are both similarities and differences between the peripheral and central nervous system, it is hoped that this research may also be useful in neurodegenerative diseases.