Microsoft Word - 14OnoseEndeavours 96 G. Onose, Monica Haras Endeavours and trends in spinal cord injury repair Endeavours and trends in spinal cord injury repair (Syllabus) G. Onose, Monica Haras “Carol Davila” University of Medicine and Pharmacy, Bucharest Background - SCI current data and statistics • Prevalence and incidence worldwide • Prevalence and incidence in Romania • Average age at injury, male: female ratio - Medical and social consequences of SCIs • Clinical classifications of SCIs • Medical complications/ co-morbidities - Current therapeutic means and their limitations in SCIs - Current context of Regenerative Medicine Integrative emphases regarding limits, detrimental pathways and related targets for neuroprotection/ recovery, in SCI - Morpho-functional, inner restrictions of the CNS/ spinal cord’s post injury self- repair - Primary injuries in SCI - Secondary injuries - patho- physiological events’ cascade - targets for neuroprotection - Final (irreversible) consequences of SCIs - Current trends in SCI (experimental) therapies Integrative emphases – clinical/ therapeutic connections - “Classical” drugs, with a long history of clinical use - New/ experimental drugs/ procedures Stem cells & tissue engineering - background - Medical and social potential - Brief history of stem cell research - Spontaneous regeneration phenomena in lower vertebrates - Definition of Regenerative Medicine - Definition and clinical use of tissue engineering - Stem cells: • Definition • Classifications • Main characteristics & properties • Embryonic stem cells • Adult stem cells Regenerative Medicine in SCI repair - Main issues/ problems • Ethical concerns • The availability of suitable stem cells • The inhibitory environment of the lesioned SC, especially in chronic SCI (glial scar, cyst formation) → grafts fail to survive • Immune reactions to allografts/ xenografts • Regeneration with aberrant reconnections → neuropathic pain, spasticity • Contamination of the stem cell lines with feeder cells, bacteria and/or transfection with feeder cells genic material • High proliferative capacity of ESC → cancer risc - The role of glial scar prevention therapy (Regeneration Promoting Therapy) •Cordaneurin Romanian Neurosurgery (2011) XVIII 1: 96 – 98 97 •CordaChron •Chondroitinase ABC - Current status of preclinical and clinical research of stem cells in SCI repair •clinical studies currently underway - Human embryonic stem cells (hESCs) - Fetal stem cells: •Fetal OEG (olfactory ensheathing glia) •Fetal Schwann cells •Umbilical cord blood cells - Adult stem cells: •Mesenchymal stem cells/ Marrow Stromal Cells (MSC) •Olfactory ensheathing glia (OEG) - including of differentiated ones transplants •Schwann cells - - including of differentiated ones transplants •Adult-derived neural progenitor cells NPCs - Stem cell research at the Teaching Emergency Hospital “Bagdasar-Arseni”, Bucharest, Romania - Tissue engineering in SCI repair •Polymeric scaffolds used for spinal cord regeneration - properties •“Smart” biomaterials - characterized by stereospecificity and self-assembling - nano-scale self-assembling bio-scaffolds •Recent conceptual & technological breaktroughs: implants built by 3D- printing •RP (rapid printing) machine (for replacement organs and whole bodies) •“Direct writing” - printing implants by MAPLE-DW Conclusions Considering the complexity of SCI pathobiology, it is important to adopt multifactorial (combinatory) strategies, that may include: - (Stem) cell replacement - Long distance guidance of neural re- growth and re-connection - Advanced scaffolding/ encapsulation (for cells replacement)/ tissue re- construction - Local delivery of neuroprotective/ neurotrophic substances (e.g. scar formation inhibitors, growth factors, neurotrophins) - Surgical removal of glial scars, posttraumatic cysts - Integrated Physical therapy Acknowledgements - for their endeavors within our team - to: A. 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