Preclinical Validation of Multilevel Intraparenchymal Stem Cell Therapy in the Porcine Spinal Cord.

作者: Juanmarco Gutierrez , Jason J. Lamanna , Natalia Grin , Carl V. Hurtig , Joseph H. Miller

DOI: 10.1227/NEU.0000000000000882

关键词:

摘要: BACKGROUND Although multiple clinical trials are currently testing different stem cell therapies as treatment alternatives for many neurodegenerative diseases and spinal cord injury, the optimal injection parameters have not yet been defined. OBJECTIVE To test cord's tolerance to increasing volumes numbers of injections in pig. METHODS Twenty-seven female Gottingen minipigs received human neural progenitor using a stereotactic platform device. Cell transplantation groups 1 5 (5-7 pigs each) was undertaken with intent assessing safety an volume escalation (10, 25, 50 µL) number (20, 30, 40 injections). Motor function general morbidity were assessed 21 days. Full necropsy performed; cords analyzed graft survival microscopic tissue damage. RESULTS No mortality or permanent surgical complications observed during 21-day study period. All animals returned preoperative baseline within 14 days, showing complete motor recovery. The histological analysis showed that there no significant decrease neuronal density between groups, engraftment ranged from 12% 31% depending on paradigm. However, damage identified when injecting large into (50 μL). CONCLUSION This series supports functional various gives critical insight important thresholds. These results relevant all translational programs delivering therapeutics cord.

参考文章(43)
Kaoru Saijo, Andrea Crotti, Christopher K. Glass, Nuclear Receptors, Inflammation, and Neurodegenerative Diseases Advances in Immunology. ,vol. 106, pp. 21- 59 ,(2010) , 10.1016/S0065-2776(10)06002-5
Allison D. Ebert, Erin L. McMillan, Clive N. Svendsen, Isolating, expanding, and infecting human and rodent fetal neural progenitor cells. Current protocols in stem cell biology. ,vol. 6, ,(2008) , 10.1002/9780470151808.SC02D02S6
Tandis Vazin, William J. Freed, Human embryonic stem cells: Derivation, culture, and differentiation: A review Restorative Neurology and Neuroscience. ,vol. 28, pp. 589- 603 ,(2010) , 10.3233/RNN-2010-0543
Jonathan Riley, John Butler, Kenneth B. Baker, Shearwood McClelland III, Qingshan Teng, Jun Yang, Mary Garrity-Moses, Thais Federici, Nicholas M. Boulis, Targeted Spinal Cord Therapeutics Delivery: Stabilized Platform and Microelectrode Recording Guidance Validation Stereotactic and Functional Neurosurgery. ,vol. 86, pp. 67- 74 ,(2008) , 10.1159/000112426
Nicholas M. Boulis, Thais Federici, Jonathan D. Glass, J. Simon Lunn, Stacey A. Sakowski, Eva L. Feldman, Translational stem cell therapy for amyotrophic lateral sclerosis Nature Reviews Neurology. ,vol. 8, pp. 172- 176 ,(2012) , 10.1038/NRNEUROL.2011.191
Jonathan Riley, Jonathan Glass, Eva L. Feldman, Meraida Polak, Jane Bordeau, Thais Federici, Karl Johe, Nicholas M. Boulis, Intraspinal stem cell transplantation in amyotrophic lateral sclerosis: a phase I trial, cervical microinjection, and final surgical safety outcomes. Neurosurgery. ,vol. 74, pp. 77- 87 ,(2014) , 10.1227/NEU.0000000000000156
Jason J Lamanna, Joseph H Miller, Jonathan P Riley, Carl V Hurtig, Nicholas M Boulis, Cellular therapeutics delivery to the spinal cord: technical considerations for clinical application Therapeutic Delivery. ,vol. 4, pp. 1397- 1410 ,(2013) , 10.4155/TDE.13.111
Gyaandeo S Maharajh, Edward A Pascoe, William C Halliday, Hilary P Grocott, Darren B Thiessen, Linda G Girling, Mary S Cheang, W Alan C Mutch, J Paul Muizelaar, Neurological Outcome in a Porcine Model of Descending Thoracic Aortic Surgery: Left Atrial–Femoral Artery Bypass Versus Clamp/Repair Stroke. ,vol. 27, pp. 2095- 2101 ,(1996) , 10.1161/01.STR.27.11.2095
V. Silani, C. Calzarossa, L. Cova, N. Ticozzi, Stem cells in amyotrophic lateral sclerosis: motor neuron protection or replacement? Cns & Neurological Disorders-drug Targets. ,vol. 9, pp. 314- 324 ,(2010) , 10.2174/187152710791292666
H. J. G. Gundersen, E. B. Jensen, The efficiency of systematic sampling in stereology and its prediction Journal of Microscopy. ,vol. 147, pp. 229- 263 ,(1987) , 10.1111/J.1365-2818.1987.TB02837.X