Spinal cord injury (SCI) is a result of initial trauma leading to secondary damage, including reduced blood flow, ischemia, and cell loss. One therapeutic approach to repair the chronically-injured spinal cord is to replace the lost cells by delivering neural stem cells (NSCs). NSCs have the ability to differentiate into the 3 main cell types of the central nervous system: astrocytes, oligodendrocytes, and neurons. These cells can aid in spinal cord repair and regeneration by secreting trophic factors, remyelinating bare axons, or establishing new neuronal connections. Our approach is to develop an optimized biomaterial-based cell-carrier formulation and implantation strategy to deliver Bioengineered Neural Trails™ to help reconnect the spinal cord through the formation of newly created neuronal circuits.
It is well known that for NSCs to appropriately differentiate and project neural processes, a substrate is required. Biomaterial scaffolds come in many shapes and sizes and are intelligently designed for specific therapeutic applications. InVivo Therapeutics is developing a proprietary biomaterial-based injectable scaffold that allows for easy delivery, promotes cell viability, facilitates cell outgrowth, and encourages transplanted cell connectivity with viable host-tissue with the goal to re-establish function across a chronic injury.
Optimal delivery of NSCs is required to minimize surgical damage and effectively localize cells at the desired regions within the spinal cord. We are moving progressively with the neurosurgical field toward the development of next-generation, minimally-invasive techniques to deliver NSCs. Conventional cell delivery to the spinal cord involves multiple perpendicular bolus injections of undifferentiated cell suspension around an injury site. Our patented delivery approach includes the creation of longitudinal cell trails within the spinal cord that traverse the injury site and promote connectivity across the gap.
InVivo Therapeutics is taking a differentiated approach to cell delivery for chronic spinal cord injury treatment. Our therapy includes an injectable biomaterial-based scaffold as a preferred NSC carrier and the creation of longitudinal cell trails across an injury site within the spinal cord. Further, we aim to partner with a stem cell company to accelerate project timelines. The advantages of our approach compared to what others have tried clinically and pre-clinically are:
Our preclinical objective is to demonstrate long-term viability of homogenous cell trails where the cells grow out of the transplanted environment and make functional connections with host cells. We believe this is a foundational requirement for re-establishing function in individuals with chronic injuries. We aim to use both in vitro and in vivo evaluation methods to efficiently determine the optimal formulation and delivery method suited for clinical translation. This preclinical program consists of three important components:
Neural stem cells: InVivo aims to use human fetal neural stem cells that are capable of differentiating into the three main cell types of the central nervous system: astrocytes, oligodendrocytes, and neurons. Methods will be developed to obtain controlled in vivo differentiation of the preferred cell subtype to maximize efficacy. InVivo further aims to partner with a stem cell company to accelerate project timelines.
Injectable scaffold: InVivo plans to use a novel biomaterial formulation for injection. This composition will be amenable to minimally-invasive, injectable cell delivery; provide a hospitable environment for cell survival, growth, and differentiation; and subsequently be degraded by physiological processes.
Injection device: InVivo has licensed proprietary technology from the University of California, San Diego that facilitates the creation of cell trails within a spinal cord. This delivery device will be tested in collaboration with renowned neurosurgeons and refined as needed to provide safe and effective delivery of cell trails within an injectable biomaterial scaffold.
This approach results in a homogenous distribution of connected neurons that can grow out into a surrounding substrate at 4 days in culture.
Further, when translated in vivo in a rat spinal cord, the cells remain viable and begin extending processes in response to their local environment.
Previous work by InVivo Therapeutics co-founders using biomaterials and neural stem cells has demonstrated promise in hemisection acute spinal cord injury models, further validating the combination therapeutic approach.
Mouse Neural Stem Cells in Rat Hemisection Model1
The preclinical study that the company was founded around investigated the use of a scaffold loaded with mouse neural stem cells (NSCs) in rats with surgically-induced unilateral spinal cord hemisection injury. In this experiment, cells alone provided minimal benefit, but the localization and support provided by the scaffold allowed for the unlocking of the NSCs’ therapeutic potential.
1. Teng YD, et al. Proc Natl Acad Sci U S A. 2002;99:3024-3029.