Promoting neural progenitor cell integration and migration in a model of chronic spinal cord injury
Neural precursor cells (NPCs) are somatic stem cells of the central nervous system, characterized by their capacity for self-renewal and their multilineage potential. In the Feb 3 edition of the Journal of Neuroscience, Drs. Michael Fehlings, Soheila Karimi-Abdolrezaee and colleagues showed that chondroitin sulfate proteoglycans (CSPGs), present in the glial scar surrounding a site of chronic spinal cord injury (SCI), negatively influence the long-term survival and integration of transplanted NPCs.
Fehlings’ group used chondroitinase ABC (ChABC) to antagonize the negative effects of CSPGs in a chronic model of compressive SCI in rodents. CSPGs were degraded following the addition of ChABC for 7 days, six weeks after injury. Mice were then treated with a transplantation of YFP-NPCs and an infusion of epidermal, fibroblast and platelet-derived growth factors previously shown to enhance NPC survival and integration (EGF, bFGF, PDGF-AA). Nine weeks following transplantation, the ChABC-treated group showed a 5.7-fold increase in the number of surviving YFP-NPCs compared to controls as well as enhanced migration of NPCs from the injection sites and differentiation along an oligodendroglial lineage, with no enhancement of posttraumatic neuropathic pain sensitivity as a result of NPC transplantation.
Perturbing CSPGs promoted successful integration and extensive migration of NPCs within the host spinal cord, followed by differentiation into oligodendrocytes. These findings are an important step in bringing investigators closer to the application of NPCs for the treatment of patients suffering from chronic SCI or other conditions characterized by a glial scar.
Synergistic effects of transplanted adult neural stem/progenitor cells, chondroitinase and growth factors promote functional repair and plasticity of the chronically injured spinal cord. Karimi-Abdolrezaee S, Eftekharpour E, Wang J, Schut D, Fehlings MG. J Neurosci. 2010 February 3. [Abstract]
CIHR Experts Discuss the Potential Health Effects of Sports
Dr. Michael Fehlings was one of six CIHR experts providing advice on sports and health in a forum titled “Bruises, Betting and Beer” on the eve of the Super Bowl. Topics included issues surrounding alcohol abuse, gambling addictions and musculoskeletal and neurological health. The title of Dr. Fehlings’ topic was: “We can rebuild him, we have the technology: Multi-disciplinary research advancements in spinal cord injury repair”.
CIHR Grants Awarded
Congratulations to McEwen investigators for their success in the latest round of CIHR Operating Grants! Funding was awarded to: Dr. Freda Miller, for her project titled “Aging and degeneration in the mammalian nervous system: role of the p53 family”, Dr. Andras Nagy for “Somatic cell reprogramming and therapeutics” and Dr. Ren-Ke Li for his project: “Harnessing the immune system to achieve cardiac restoration by allogeneic cell transplantation”.
March 17, 2010 - Matthew Bjerknes Department of Medical Biophysics, University of Toronto
Cell Lineage Metastability
Location and Time: Red Seminar Room, 2nd Floor, TDCCBR Building, 160 College Street, 5-6pm
Recent Publications
Development and function of myeloid-derived suppressor cells generated from mouse embryonic and hematopoietic stem cells. Zhou Z, French DL, Ma G, Eisenstein S, Chen Y, Divino CM, Keller G, Chen SH, Pan PY. Stem Cells. 2010 January 13. [Abstract]
Genetic deletion or pharmacological inhibition of dipeptidyl peptidase-4 improves cardiovascular outcomes following myocardial infarction in mice. Sauvé M, Ban K, Momen A, Zhou YQ, Henkelman RM, Husain M, Drucker DJ. Diabetes. 2010 Jan 22. [Abstract]
Sepsis-induced myocardial depression is associated with transcriptional changes in energy metabolism and contractile related genes: A physiological and gene expression-based approach. Dos Santos CC, Gattas DJ, Tsoporis JN, Smedding L, Kabir G, Masoom H, Akram A, Plotz F, Slutsky AS, Husain M, Sibbald WJ, Parker TG. Crit Care Med. 2010 January 22. [Abstract]
Vascular endothelial growth factor - a positive and negative regulator of tumor growth. Vecchiarelli-Federico LM, Cervi D, Haeri M, Li Y, Nagy A, Ben-David Y. Cancer Res. 2010 January 26. [Abstract]
Bone marrow-derived human hematopoietic stem cells engraft NOD/SCID mice and traffic appropriately to an inflammatory stimulus in the joint. Chang NH, Inman RD, Dick JE, Wither JE. J Rheumatol. 2010 January 28. [Abstract]
Poly(ethylene glycol) modification enhances penetration of fibroblast growth factor 2 to injured spinal cord tissue from an intrathecal delivery system. Kang CE, Tator CH, Shoichet MS. J Control Release. 2010 January 28. [Abstract]
Growth differentiation factor 5 regulates cardiac repair after myocardial infarction. Zaidi SH, Huang Q, Momen A, Riazi A, Husain M. J Am Coll Cardiol. 2010 January. [Abstract]
Thromboprophylaxis in traumatic and elective spinal surgery: Analysis of questionnaire response and current practice of spine trauma surgeons. Ploumis A, Ponnappan RK, Sarbello J, Dvorak M, Fehlings MG, Baron E, Anand N, Okonkwo DO, Patel A, Vaccaro AR. Spine. 2010 February 1. [Abstract]
The McEwen Centre for Regenerative Medicine, led by director Dr. Gordon Keller, includes 15 scientists at the University of Toronto and five Toronto hospitals, working to advance the development of more effective treatments for conditions including heart disease, diabetes, respiratory disease and spinal cord injury.
The Centre is located at University Health Network, MaRS Centre, Toronto Medical Discovery Tower, 101 College Street, 8th Floor, Room 701, Toronto, Ontario, Canada M5G 1L7
Email: mcewencentre@uhn.on.ca
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