Preclinical Validation of Multilevel Intraparenchymal Stem Cell Therapy in the Porcine Spinal Cord
| Autor: | Jonathan Riley, Juanmarco Gutierrez, Pablo Avalos, Joseph H. Miller, Lindsey N. Urquia, Nicholas M. Boulis, Jason J. Lamanna, Thais Federici, Natalia Grin, Carl V. Hurtig, Clive N. Svendsen |
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| Rok vydání: | 2015 |
| Předmět: |
Microinjections
Swine medicine.medical_treatment Cell Neural Stem Cells Animals Humans Medicine Progenitor cell Spinal cord injury Injections Spinal Spinal Cord Injuries business.industry Graft Survival Stem-cell therapy medicine.disease Spinal cord Transplantation Clinical trial medicine.anatomical_structure Spinal Cord Anesthesia Swine Miniature Female Surgery Neurology (clinical) Stem cell business Stem Cell Transplantation |
| Zdroj: | Neurosurgery. 77:604-612 |
| ISSN: | 0148-396X |
| Popis: | 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 the spinal cord's tolerance to increasing volumes and numbers of stem cell injections in the pig. METHODS Twenty-seven female Gottingen minipigs received human neural progenitor cell injections using a stereotactic platform device. Cell transplantation in groups 1 to 5 (5-7 pigs in each) was undertaken with the intent of assessing the safety of an injection volume escalation (10, 25, and 50 µL) and an injection number escalation (20, 30, and 40 injections). Motor function and general morbidity were assessed for 21 days. Full necropsy was performed; spinal cords were analyzed for graft survival and microscopic tissue damage. RESULTS No mortality or permanent surgical complications were observed during the 21-day study period. All animals returned to preoperative baseline within 14 days, showing complete motor function recovery. The histological analysis showed that there was no significant decrease in neuronal density between groups, and cell engraftment ranged from 12% to 31% depending on the injection paradigm. However, tissue damage was identified when injecting large volumes into the spinal cord (50 μL). CONCLUSION This series supports the functional safety of various injection volumes and numbers in the spinal cord and gives critical insight into important safety thresholds. These results are relevant to all translational programs delivering cell therapeutics to the spinal cord. |
| Databáze: | OpenAIRE |
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