Abstract
Cell therapy for central nervous system (CNS) disorders is beginning to prove its safety and efficiency. Intraparenchymal transplantation can be an option for cell delivery; however, one concern regarding this method is that the transplantation cannula may cause additional brain injuries. These include vessel damage, which results in brain hemorrhage, and clogging of the cannula by brain debris and/or cell clusters, which requires replacement of the cannula or forced injection causing jet flow of the cell suspension. We compared cannulas for cell delivery used in clinical trials, the Pittsburg and Mizuho cannulas, to a newly designed one, MK01, to assess their usability. MK01 has a spherical-shaped tip with a fan-like open orifice on the side of the cannula, which prevents vessel damage, clogging of brain debris, and jet flow phenomenon. We compared the extent of rat cervical and abdominal arterial damage with the cannula, the amount of debris in the cannula, the force needed to cause jet flow, and cell viability. While the viability of cells passed through the cannulas was almost the same among cannulas (approximately 95%), the Pittsburg cannula caused cervical arterial injury and subsequent hemorrhage, as it required a significantly smaller force to penetrate the arterial wall. Moreover, the Pittsburg cannula, but not the Mizuho and MK01 cannulas, showed high frequency of brain debris in the needle tip (approximately 80%) after brain puncture. While jet flow of the injection liquid was observed even when using smaller forces in the Pittsburg and Mizuho cannulas, MK01 constantly showed low jet flow occurrence. Thus, MK01 seems to be safer than the previously reported cannulas, although further investigation is necessary to validate its safety for clinical use.
Highlights
Transplantation of stem cells for central nervous system (CNS) disease has shown promising results in the laboratory [1,2,3], and several clinical trials are beginning to prove its safety and efficacy [4,5,6,7]
An ideal transplantation route has not been determined yet, intraparenchymal transplantation remains an option for cell delivery, since it enables delivery of a sufficient amount of cells into the damaged brain compared to that achieved with intravascular transplantation [6, 8, 9]
No cannula has been approved for cell transplantation by regulatory agencies, including the FDA, and different types of cannulas specially designed or adopted from other uses are being used for clinical trials [6, 10]
Summary
Transplantation of stem cells for central nervous system (CNS) disease has shown promising results in the laboratory [1,2,3], and several clinical trials are beginning to prove its safety and efficacy [4,5,6,7]. The risk of brain hemorrhage by electrode insertion during deep brain stimulation surgery is reported to be at approximately 2-5%, throughout the procedure [11], and stem cell transplantation presumably has similar or higher risk of such complication, as the cannula is inserted into brain areas with preexisting damages [6, 12]. Another concern is that brain debris and cell suspension may cause clogging of the cannula, since most stem cell types have adherence properties, and the cells are kept in a stabilized position for a while after delivery to the operation room. We evaluated the design and performance of this novel cannula in comparison with cannulas used in clinical trials
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
