{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T03:04:29Z","timestamp":1789700669557,"version":"4.0.1"},"reference-count":31,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"6","license":[{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,1]]},"abstract":"<jats:sec>\n<jats:title>OBJECTIVE<\/jats:title>\n<jats:p>The objective of this study was to develop and evaluate the feasibility and safety of a novel transaxial surgical approach for the delivery of human induced pluripotent stem cell\u2013derived dopaminergic neuroprogenitor cells (DANPCs) into the putamen nucleus using nonhuman primates and surgical techniques and tools relevant to human clinical translation.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>METHODS<\/jats:title>\n<jats:p>Nine immunosuppressed, unlesioned adult cynomolgus macaques (4 females, 5 males) received intraputaminal injections of vehicle or DANPCs (0.9 \u00d7 10<jats:sup>5<\/jats:sup> to 1.1 \u00d7 10<jats:sup>5<\/jats:sup> cells\/\u00b5L) under real-time intraoperative MRI guidance. The infusates were combined with 1-mM gadoteridol (for intraoperative MRI visualization) and delivered via two tracks per hemisphere (ventral and dorsal) using a transaxial approach. The total volumes of infusion were 25 \u00b5L and 50 \u00b5L for the right and left putamen, respectively (infusion rate 2.5 \u00b5L\/min). Animals were evaluated with a battery of clinical and behavioral outcome measures and euthanized 7 or 30 days postsurgery; full necropsies were performed by a board-certified veterinary pathologist. Brain tissues were collected and processed for immunohistochemistry, including against the human-specific marker STEM121.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>RESULTS<\/jats:title>\n<jats:p>The optimized surgical technique and tools produced successful targeting of the putamen via the transaxial approach. Intraoperative MR images confirmed on-target intraputaminal injections in all animals. All animals survived to scheduled termination without clinical evidence of neurological deficits. The first 4 animals to undergo surgery had mild brain swelling noted at the end of surgery, of which 3 had transient reduced vision; administration of mannitol therapy and reduced intravenous fluid during the surgical procedure addressed these complications. Immunostaining against STEM121 confirmed the presence of grafted cells along the injection track within the targeted putamen area of DANPC-treated animals. All adverse histological findings were limited in scope and consistent with surgical manipulation, injection procedure, and postsurgical inflammatory response to the mechanical disruption caused by the cannula insertion.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>CONCLUSIONS<\/jats:title>\n<jats:p>The delivery system, injection procedure, and DANPCs were well tolerated in all animals. Prevention of mild brain swelling by mannitol dosing and reduction of intravenous fluids during surgery allowed visual effects to be avoided. The results of the study established that this novel transaxial approach can be used to correctly and safely target cell injections to the postcommissural putamen and support clinical investigation.<\/jats:p>\n<\/jats:sec>","DOI":"10.3171\/2024.4.jns24367","type":"journal-article","created":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T01:35:53Z","timestamp":1722044153000},"page":"1554-1566","source":"Crossref","is-referenced-by-count":8,"title":["Preclinical evaluation of transaxial intraputaminal trajectory for enhanced distribution of grafted cells in Parkinson\u2019s disease"],"prefix":"10.3171","volume":"141","author":[{"given":"Marina E.","family":"Emborg","sequence":"first","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison, Wisconsin;"},{"name":"Departments of Medical Physics,"},{"name":"Cellular and Molecular Pathology Graduate Program, University of Wisconsin\u2013Madison, Wisconsin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Mancinelli","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison, Wisconsin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia C.","family":"Colwell","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison, Wisconsin;"},{"name":"Cellular and Molecular Pathology Graduate Program, University of Wisconsin\u2013Madison, Wisconsin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra D.","family":"Zinnen","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison, Wisconsin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Pape","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison, Wisconsin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Brunner","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison, Wisconsin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoriya","family":"Bondarenko","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison, Wisconsin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey","family":"Fitz","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison, Wisconsin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Coonen","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison, Wisconsin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktorie","family":"Menna","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison, Wisconsin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerri","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison, Wisconsin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Schultz-Darken","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison, Wisconsin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather A.","family":"Simmons","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison, Wisconsin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha","family":"Tran","sequence":"additional","affiliation":[{"name":"Aspen Neuroscience Inc., San Diego, California; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Larson","sequence":"additional","affiliation":[{"name":"Neurosurgery, Department of Medicine, University of Arizona, Tucson, Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miles","family":"Olsen","sequence":"additional","affiliation":[{"name":"Psychiatry, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Hurley","sequence":"additional","affiliation":[{"name":"Radiology, University of Wisconsin\u2013Madison, Wisconsin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres M.","family":"Bratt-Leal","sequence":"additional","affiliation":[{"name":"Aspen Neuroscience Inc., San Diego, California; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Wirth","sequence":"additional","affiliation":[{"name":"Aspen Neuroscience Inc., San Diego, California; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanette M.","family":"Metzger","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison, Wisconsin;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"issue":"4","key":"b1","series-title":"Nat Biomed Eng","first-page":"370","article-title":"Challenges in the clinical advancement of cell therapies for Parkinson\u2019s disease","volume":"7","author":"Skidmore S","year":"2023","unstructured":"Skidmore S, Barker RA. 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