Engraftment,migration and differentiation of neural stem cells in the rat spinal cord following contusion injury |
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Authors: | Siobhan S. McMahon Silke Albermann Gemma E. Rooney Georgina Shaw Yolanda Garcia Eva Sweeney Jacqueline Hynes Peter Dockery Timothy O'Brien Anthony J. Windebank Timothy E. Allsopp Frank P. Barry |
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Affiliation: | 1. Department of Anatomy, National University of Ireland, Galway, Ireland;2. Regenerative Medicine Institute, National University of Ireland, Galway, Ireland;3. Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA;4. Pfizer Regenerative Medicine, Granta Park, Cambridge, UK;2. Current address: Pfizer Regenerative Medicine, Granta Park, Cambridge, UK;1. Krembil Neuroscience Center, University Health Network, Toronto Western Hospital, Toronto, ON M5T 2S8, Canada;2. Institutes of Medical Science, University of Toronto, University Health Network Toronto, ON M5S 1A8, Canada;1. Department of Surgical, Medical, Dental and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy;2. Obstetrics and Gynecology Unit, Department of Obstetrics, Gynecology and Pediatrics, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy;3. Institute of Reproductive and Developmental Biology, Imperial College London, United Kingdom;4. Prenatal Cell and Gene Therapy Group, Institute for Women''s Health, University College London, London, United Kingdom;5. Department of Paediatric Pathology, Camelia Botnar Laboratories, Great Ormond Street Hospital, London, United Kingdom;6. Surgery Unit, UCL Institute of Child Health, London, United Kingdom;1. Biology Department, Science and Research Branch, Islamic Azad University, Tehran, Iran;2. Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran;3. Department of Biology, School of Sciences, University of Isfahan, Isfahan, Iran;4. Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;5. Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran |
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Abstract: | Background aimsSpinal cord injury is a devastating injury that impacts drastically on the victim's quality of life. Stem cells have been proposed as a therapeutic strategy. Neural stem (NS) cells have been harvested from embryonic mouse forebrain and cultured as adherent cells. These NS cells express markers of neurogenic radial glia.MethodsMouse NS cells expressing green fluorescent protein (GFP) were transplanted into immunosupressed rat spinal cords following moderate contusion injury at T9. Animals were left for 2 and 6 weeks then spinal cords were fixed, cryosectioned and analyzed. Stereologic methods were used to estimate the volume and cellular environment of the lesions. Engraftment, migration and differentiation of NS cells were also examined.ResultsNS cells integrated well into host tissue and appeared to migrate toward the lesion site. They expressed markers of neurons, astrocytes and oligodendrocytes at 2 weeks post-transplantation and markers of neurons and astrocytes at the 6-week time-point. NS cells appeared to have a similar morphologic phenotype to radial glia, in particular at the pial surface.ConclusionsAlthough no functional recovery was observed using the Basso Beattie Bresnahan (BBB) locomotor rating scale, NS cells are a potential cellular therapy for treatment of injured spinal cord. They may be used as delivery vehicles for therapeutic proteins because they show an ability to migrate toward the site of a lesion. They may also be used to replace lost or damaged neurons and oligodendrocytes. |
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