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G. Solcan 1 ., M. Musteaţă 1 , S. Iencean 2

REGENERATIVE THERAPY IN SPINAL CORD INJURIES: TRANSPLANT OF OLFACTORY ENHANCED GLIA, STEM CELLS AND OVEREXPRESSING SCHWANN CELLS. G. Solcan 1 ., M. Musteaţă 1 , S. Iencean 2 University of Agricultural Sciences and Veterinary Medicine,

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G. Solcan 1 ., M. Musteaţă 1 , S. Iencean 2

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  1. REGENERATIVE THERAPY IN SPINAL CORD INJURIES: TRANSPLANT OF OLFACTORY ENHANCED GLIA, STEM CELLS AND OVEREXPRESSING SCHWANN CELLS G. Solcan1., M. Musteaţă1, S. Iencean2 University of Agricultural Sciences and Veterinary Medicine, Faculty of Veterinary Medicine, Iasi, Romania, 8 M. Sadoveanu Alley, gsolcan@uaiasi.ro Nerosurgery Hospital “N. Oblu” Iasi

  2. Introduction • In veterinary clinics • acute SCI type I IVDD, vertebral fractures and luxation, vascular disease (e.g. fibrocartilaginous embolism (FCE) and haemorrhage), cervical stenoticmyelopathy and congenital malformation causing instability.  • chronic diseases, such as neoplasia, discospondylitis and inflammatory or infectious spinal cord disease. • Acute onset of SC dysfunction = a combination of one or more events including concussion, compression, ischemia, or laceration of the spinal cord.

  3. Patophysiology

  4. Strategy following SC injury 1. Neuroprotection: Diminution of the secondary damage 2.Neurorestauration: Remyelination, conduction 3. Neuroregeneration/Plasticity • Antagonization of inhibitoyfarctors • Axonal growth factors (neurotrophyic) 4. Axonal guidance towards site of deafferation (specific regeneration) 5. Neurorectonstruction: Cell and tissue transplantation

  5. Considerations for developing cell therapy for spinal cord regeneration • To successfully treat SCI by promoting functional recovery, • -cellular therapies must integrate into the injury site • and restore the lost neuronal circuitry or • promote plasticity of the spared neurons. • For this goal, cellular therapies should be designed • considering both the obstacles posed by the injury site • as well as sourcing and reproducibility issues associated with different cell culture systems.

  6. Obstacles to regeneration presented by the injured spinal cord - Cavity formation • bridge the lesion and restore signaling in the SC. • factors that promote regeneration of the damaged axons into the cavity while also providing the trophic support necessary for cell migration. • reduction of the cavity size = increase in functional recovery

  7. Obstacles to regeneration presented by the injured spinal cord – Glial scar • Transplanted cells = counterbalance to the inhibitory effects of the glial scar • Secretion of the extracellular matrix and • cytokines that promote cell migration • Other therapy ± cell therapy • molecules that prevent CSPG synthesis • chondroitinases which degrade the CSPGs in vivo

  8. Obstacles to regeneration presented by the injured spinal cord – Myelin based inhibitors • Strategies • Sialidase • Tenascin-R • genetic manipulation and antibodies

  9. Study and therapy in SC injury Contusions model Transection model

  10. Cells Sources Transplantable cells can be obtained from : - the patient (autologous) - genetically different individuals, embryos, or umbilical cords (allogeneic) - different species (xenogeneic) The undifferentiated nature of embryonic and umbilical cells minimizesimmunological rejection.

  11. Site of Transplantation Donor cells are transplanted in • the spinal cord • cerebro-spinal fluid • intravenously • intramuscularly

  12. Surgical practicein spinal cord injury The surgical procedure consist of - remove of spinal cord scar - implanting of bone – marrow tissue into the spinal cord injury site. The bone-marrow tissue transplantation procedure has no complications. Scar reduction make the post – injury scar more permeable to neuronal axons attempting to regrow through the injury site.

  13. Dr. Tarcisio Barros (Sao Paulo) have infused bone-marrow-derived stem cells into the spinalartery closest to the injury site Dr. Andrey Bryukhovetskiy (Moscow) has transplanted both embryonic / fetal stem cells and autologous adult stem cells Dr. K-S Kang (Seoul)injected stems cells isolated from umbilical cord blood into the injury area Dr. Yoon Ha (South Korea) has transplanted bone-marrow cells into the injury site of patients with acute SCI Dr. Eva Sykova (Prague ) have harvested autologous, bone-marrow stem cells from the iliac bone and re-introduced intravenously Dr. Yongfu Zhang (China) have transplanted autologous bone-marrow stem cells into patients with both acute and chronic SCI Bone-marrow derived stem cells

  14. Olfactory Tissueand Cell Transplantation Dr. Carlos Lima (Lisbon) implant whole olfactory tissuefrom the patient back into the injury site Dr. Hongyun Huang (Beijing) transplants OECs isolated from fetal olfactory bulbs Dr. Alan MacKay-Sim (Australia) has implanted autologous OECs backinto the patient’s injured cord Dr. Tiansheng Sun (Beijing) have transplanted OECs into patients with SCI

  15. OTHER CELL TRANSPLANTATION Dr. Fernando Ramirez (Mexico) has transplanted blue-shark, embryonic neuronal cells (xenogeneic transplantation) The Diacrin Corporation (USA) sponsored another xenotransplantation clinical trial. Dr John McDonald (Missouri) and Dr Darryl DiRisio (Albany) injected immature fetal pig, myelin cells into the cord surrounding the injury site Dr. Hui Zhu have transplanted fetal Schwann cells

  16. Thank you!

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