BACKGROUND: Only recently have data been published attempting to validate a technology and technique suitable for targeted delivery of biological payloads to the human spinal cord. OBJECTIVE: To characterize the development and evolution of a spine-stabilized microinjection platform as a vehicle for biologics delivery to the cervical and thoracolumbar spine on the basis of preclinical experience in both non-Good Laboratory Practice (GLP) experimental series and GLP studies. METHODS: Our laboratory completed > 100 cervical and lumbar porcine microinjection procedures between July 2004 and June 2010. This included both non-GLP- and GLP-adherent survival series to validate the safety and accuracy achievable with intraspinal microinjection. During this time, 3 different microinjection platforms, injection stages, and cannula designs were tested. RESULTS: Repetitive technological improvements reduced incision length, decreased procedural complexity, and simplified ventral horn targeting and accuracy. These changes reduced procedural invasiveness and the likelihood of neurological morbidity while improving targeting accuracy. In part as a result of these technological improvements and procedural modifications, we have safely progressed from single unilateral microinjections to multiple bilateral injections without long-term neurological sequelae. CONCLUSION: Technological and procedural refinements have significantly enhanced the capabilities of intraspinal microinjection-based biologics delivery. Reductions in procedural invasiveness and the capability to deliver sequential biological payloads effectively have broadened the flexibility of intraspinal microinjection to a widened array of intrinsic spinal cord pathologies. These advances have laid the groundwork for clinical translation of spinal cord microinjections.
BACKGROUND: Only recently have data been published attempting to validate a technology and technique suitable for targeted delivery of biological payloads to the human spinal cord. OBJECTIVE: To characterize the development and evolution of a spine-stabilized microinjection platform as a vehicle for biologics delivery to the cervical and thoracolumbar spine on the basis of preclinical experience in both non-Good Laboratory Practice (GLP) experimental series and GLP studies. METHODS: Our laboratory completed > 100 cervical and lumbar porcine microinjection procedures between July 2004 and June 2010. This included both non-GLP- and GLP-adherent survival series to validate the safety and accuracy achievable with intraspinal microinjection. During this time, 3 different microinjection platforms, injection stages, and cannula designs were tested. RESULTS: Repetitive technological improvements reduced incision length, decreased procedural complexity, and simplified ventral horn targeting and accuracy. These changes reduced procedural invasiveness and the likelihood of neurological morbidity while improving targeting accuracy. In part as a result of these technological improvements and procedural modifications, we have safely progressed from single unilateral microinjections to multiple bilateral injections without long-term neurological sequelae. CONCLUSION: Technological and procedural refinements have significantly enhanced the capabilities of intraspinal microinjection-based biologics delivery. Reductions in procedural invasiveness and the capability to deliver sequential biological payloads effectively have broadened the flexibility of intraspinal microinjection to a widened array of intrinsic spinal cord pathologies. These advances have laid the groundwork for clinical translation of spinal cord microinjections.
Authors: Yvette S Nout; Ephron S Rosenzweig; John H Brock; Sarah C Strand; Rod Moseanko; Stephanie Hawbecker; Sharon Zdunowski; Jessica L Nielson; Roland R Roy; Gregoire Courtine; Adam R Ferguson; V Reggie Edgerton; Michael S Beattie; Jacqueline C Bresnahan; Mark H Tuszynski Journal: Neurotherapeutics Date: 2012-04 Impact factor: 7.620
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: J Simon Lunn; Stacey A Sakowski; Thais Federici; Jonathan D Glass; Nicholas M Boulis; Eva L Feldman Journal: Regen Med Date: 2011-03 Impact factor: 3.806
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