First Human Trial of Stem Cell Transplantation in Complex Arrays for Stroke Patients Using the Intracerebral Microinjection Instrument

• Published in: Operative neurosurgery (Hagerstown, Md.) Vol. 18; no. 5; pp. 503 - 510
• Main Authors: Zhang, GuangZhu, Cunningham, Miles, Zhang, HongTian, Dai, YiWu, Zhang, Ping, Ge, GuangZhi, Wang, BeiBei, Bai, MiaoChun, Hazel, Thomas, Johe, Karl, Xu, RuXiang
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.05.2020; Wolters Kluwer Health, Inc
• Subjects: Biotechnology industry; Clinical trials; Health aspects; Homeopathy; International economic relations; Materia medica and therapeutics; Medical research; Neurosurgery; Stem cell transplantation; Stem cells; Stroke; Stroke patients; Therapeutics; Transplantation; Transplants & implants; United States; Maryland; China; Neural transplantation; Stroke; Delivery; IMI; Intracerebral Microinjection Instrument; Stem cells
• ISSN: 2332-4252; 2332-4260; 2332-4260
• DOI: 10.1093/ons/opz204

Abstract BACKGROUND In preclinical studies, the Intracerebral Microinjection Instrument (IMI) has demonstrated the ability to deliver therapeutics within the brain in 3-dimensional arrays from a single overlying penetration while incurring minimal localized trauma. OBJECTIVE To evaluate the safety and performance of the IMI in its first use in humans to deliver stem cells in complex configurations within brain regions affected by ischemic injury. METHODS As part of a phase 1 study, 3 chronically hemiparetic motor stroke patients received intracerebral grafts of the therapeutic stem cell line, NSI-566, using the IMI and its supporting surgical planning software. The patients were 37 to 54 yr old, had ischemic strokes more than 1 yr prior to transplantation, and received Fugl-Meyer motor scale scores of 17-48 at screening. During a single surgical procedure, patients received several neural grafts (42 ± 3) within the peri-infarct region targeted strategically to facilitate neural repair. RESULTS The IMI enabled multiple cellular deposits to be safely placed peripheral to stroke lesions. The procedure was well tolerated, recovery was uneventful, and there occurred no subsequent complications. The IMI performed reliably throughout the procedures without evident targeting errors. One year after transplantation, all 3 subjects displayed significant clinical improvement, and imaging analysis demonstrated occupation of infarct cavities with new tissue without tumor formation. CONCLUSION IMI technology permits unprecedented numbers of injections to be tactically placed in 3-dimensional arrays safely and reliably in human subjects. This advanced methodology can optimize the benefits of novel therapeutics by enabling versatile 3-dimensional intracerebral targeting.