Feasibility of Three-Dimensional Placement of Human Therapeutic Stem Cells Using the Intracerebral Microinjection Instrument

Abstract

The ability to safely place viable intracerebral grafts of human-derived therapeutic stem cells in three-dimensional (3D) space was assessed in a porcine model of human stereotactic surgery using the Intracerebral Microinjection Instrument (IMI) compared to a conventional straight cannula. Two groups of healthy minipigs received injections of the human stem cell line, NSI-566, into the right hemisphere and cell suspension carrier media into the left hemisphere. Group A received all injections using a straight, 21-gauge stainless steel cannula. Group B received all injections using the IMI, whereby radial distribution of injections was achieved via angular extension of a 196-micron diameter cannula from a single overlying penetration of the guide cannula. Each animal received six 20 µL intracerebral-injections within each hemisphere: three in a radial distribution, covering a 180° arc with each injection separated by a 60° arc distance, within both frontal cortex and basal ganglia. H&E and immunocytochemistry (HuNu and GFAP) were used to identify implanted cells and to assess tissue response. The presence of surviving cells in appropriate brain regions demonstrated that the IMI is capable of accurately delivering viable human-derived stem cells safely in a 3D array at predetermined sites within the pig brain. In addition, qualitative evaluation of the target tissue suggests efficient delivery with decreased surgical trauma. In contrast to traditional straight cannulas, the IMI enables the delivery of multiple precise cellular injection volumes in accurate 3D arrays. In this porcine large animal model of human neurosurgery, the IMI reduced surgical time and appeared to reduce neural trauma associated with multiple penetrations that would otherwise be required using a conventional straight delivery cannula.