STUDY DESIGN: Assessment of long-term surgical risks from multiple intraspinal cell injections. OBJECTIVE: To prove that multilevel-targeted cell injection to the spinal cord can be a feasible and safe procedure. SUMMARY OF BACKGROUND DATA: Neural cell transplantation has been proposed as a treatment for a variety of neurologic disorders, including degenerative, ischemic, autoimmune, and traumatic etiologies. Among these diseases, the lack of effective treatment for amyotrophic lateral sclerosis has prompted the search for cell-based neuroprotection or motor neuron-replacement therapies. METHODS: Fifteen female minipigs, divided into 3 experimental groups, underwent either 5 or 10 unilateral injections of neural stem cells or 10 vehicle injections into the C3-C5 segments of the spinal cord, using a device and technique developed for safe and accurate injection into the human spinal cord. All animals received intravenous Tacrolimus (0.025 mg/kg) BID during the course of the study. Sensory and motor functions as well as general morbidity were assessed for 28 days. Full necropsy was performed and spinal cords were analyzed for graft survival. This study was performed under Good Laboratory Practice conditions. RESULTS: Neither mortality nor permanent surgical complications were observed within the 28-day study period. All animals returned to preoperative baseline showing full motor function recovery. Graft survival was demonstrated by immunohistochemistry. CONCLUSION: Clinically acceptable neural progenitor survival, distribution, and density were achieved using the number of injections and surgical techniques specifically developed for this purpose.
STUDY DESIGN: Assessment of long-term surgical risks from multiple intraspinal cell injections. OBJECTIVE: To prove that multilevel-targeted cell injection to the spinal cord can be a feasible and safe procedure. SUMMARY OF BACKGROUND DATA: Neural cell transplantation has been proposed as a treatment for a variety of neurologic disorders, including degenerative, ischemic, autoimmune, and traumatic etiologies. Among these diseases, the lack of effective treatment for amyotrophic lateral sclerosis has prompted the search for cell-based neuroprotection or motor neuron-replacement therapies. METHODS: Fifteen female minipigs, divided into 3 experimental groups, underwent either 5 or 10 unilateral injections of neural stem cells or 10 vehicle injections into the C3-C5 segments of the spinal cord, using a device and technique developed for safe and accurate injection into the human spinal cord. All animals received intravenous Tacrolimus (0.025 mg/kg) BID during the course of the study. Sensory and motor functions as well as general morbidity were assessed for 28 days. Full necropsy was performed and spinal cords were analyzed for graft survival. This study was performed under Good Laboratory Practice conditions. RESULTS: Neither mortality nor permanent surgical complications were observed within the 28-day study period. All animals returned to preoperative baseline showing full motor function recovery. Graft survival was demonstrated by immunohistochemistry. CONCLUSION: Clinically acceptable neural progenitor survival, distribution, and density were achieved using the number of injections and surgical techniques specifically developed for this purpose.
Authors: Jonathan D Glass; Vicki S Hertzberg; Nicholas M Boulis; Jonathan Riley; Thais Federici; Meraida Polak; Jane Bordeau; Christina Fournier; Karl Johe; Tom Hazel; Merit Cudkowicz; Nazem Atassi; Lawrence F Borges; Seward B Rutkove; Jayna Duell; Parag G Patil; Stephen A Goutman; Eva L Feldman Journal: Neurology Date: 2016-06-29 Impact factor: 9.910
Authors: Jason J Lamanna; Lindsey N Urquia; Carl V Hurtig; Juanmarco Gutierrez; Cody Anderson; Pete Piferi; Thais Federici; John N Oshinski; Nicholas M Boulis Journal: Stereotact Funct Neurosurg Date: 2017-01-28 Impact factor: 1.875
Authors: Nicholas M Boulis; Thais Federici; Jonathan D Glass; J Simon Lunn; Stacey A Sakowski; Eva L Feldman Journal: Nat Rev Neurol Date: 2011-12-13 Impact factor: 42.937
Authors: Thais Federici; Carl V Hurtig; Kentrell L Burks; Jonathan P Riley; Vibhor Krishna; Brandon A Miller; Eric A Sribnick; Joseph H Miller; Natalia Grin; Jason J Lamanna; Nicholas M Boulis Journal: J Vis Exp Date: 2012-12-07 Impact factor: 1.355