Cervical multilevel intraspinal stem cell therapy: Assessment of surgical risks in gottingen minipigs

Bethwel Raore, Thais Federici, Jason Taub, Michael C. Wu, Jonathan Riley, Colin K. Franz, Michele A. Kliem, Brooke Snyder, Eva L. Feldman, Karl Johe, Nicholas M. Boulis

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

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.

Original languageEnglish (US)
JournalSpine
Volume36
Issue number3
DOIs
StatePublished - Feb 1 2011

Keywords

  • Microinjection
  • cell therapy
  • neural stem cells
  • pigs
  • spinal cord

ASJC Scopus subject areas

  • Clinical Neurology
  • Orthopedics and Sports Medicine

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