Devices for cell transplantation into the central nervous system: Design considerations and emerging technologies

Abstract

Successful use of cell-based therapies for the treatment of neurological diseases is dependent upon effective delivery to the central nervous system (CNS). The CNS poses several challenges to the delivery of cell-based therapeutics, including the blood–brain barrier, anatomic complexity, and regional specificity. Targeted delivery methods are therefore required for the selective treatment of specific CNS regions. In addition, CNS tissues are mechanically and physiologically delicate and even minor injury to normal brain or spinal cord can cause devastating neurological deficits. Targeted delivery methods must therefore minimize tissue trauma. At present, direct injection into brain or spinal cord parenchyma promises to be the most versatile and accurate method of targeted CNS therapeutic delivery. While direct injection methods have already been employed in clinical trials of cell transplantation for a wide variety of neurological diseases, there are many shortcomings with the devices and surgical approaches currently used. Some of these technical limitations may hinder the clinical development of cell transplantation therapies despite validity of the underlying biological mechanisms. In this review, we discuss some of the important technical considerations of CNS injection devices such as targeting accuracy, distribution of infused therapeutic, and overall safety to the patient. We also introduce and discuss an emerging technology – radially branched deployment – that may improve our ability to safely distribute cell-based therapies and other therapeutic agents to the CNS. Finally, we speculate on future technological developments that may further enhance the efficacy of CNS therapeutic delivery.

Stem Cell–Based Tissue Replacement After Stroke

“…intraparenchymal, intraventricular) or intraarterial cell delivery, respectively. While stereotaxic cell transplantation comes at a small, but considerable risk of secondary damage 98 , intraarterial administration of larger cells such as MSCs or the application excessive cell numbers may lead to secondary infarctions 99, 100 . While this risk is not apparent for smaller cell populations such as MNCs or GPs 99 , those may be in turn pass cerebral circulation in significant numbers without reaching their primary site of action.…”

Transplantation of stem cell-derived astrocytes for the treatment of amyotrophic lateral sclerosis and spinal cord injury

“…As both ALS and SCI affect long segments of spinal cord (several millimeters long and sometimes independent regions within the cord), a need for multiple injections adds to the complexity of the procedure. Aware of this issue, neurosurgeons are developing new surgical techniques or tools (e.g., radially-branched cannulae) able to deliver therapeutic agents to large CNS areas in a single shot [125] . Other attempts to find the optimal delivery route used intranasal [126] , intrathecal [127][128][129] , intraperitoneal [130] , intramuscular [131] , intravenous [132][133][134][135] and intra-bone marrow cell [136] transplantation.…”

Preclinical development of an automated injection device for intradermal delivery of a cell-based therapy

“…From a clinical perspective, this would give the clinician the confidence that the cell product would remain viable within the delivery system even at prolonged treatment times. Another important factor to consider is that cell sedimentation is likely to occur within the syringe and tubing during dosing of multiple injections if the device is left stationary for prolonged periods of time [ 33 ]. As a result, the first ejections could contain more cells than those dispensed at the end.…”