Research Studies
Spine

The Department of Neurological Surgery is currently conducting the following studies in Spine:

• Neural Regeneration in Models of Spinal Cord Injury and Glaucoma
• Stem Cell-Derived Astrocytes as a Transplantable Resource for Spinal Cord Lesion Repair and Plasticity
• The Adult Neural Stem Cell and Spinal Cord Remodeling

Neural Regeneration in Models of Spinal Cord Injury and Glaucoma

Principal Investigator: Philip Horner, PhD
Funded By: Glaucoma Research Foundation (Catalyst for a Cure)

A major focus is neural regeneration in models of spinal cord injury and Glaucoma. Following injury to the central nervous system, a cascade of events leads to cellular proliferation and expression of molecules that act as physical and molecular inhibitors of axon growth. Dr. Horner's lab is interested in utilizing gene therapy approaches to deliver growth promoting molecules that can stimulate axonal regeneration directly or block the effect of natural inhibitors. The ability of a neuron to regenerate its axon is determined by how the damaged axon responds to external factors found in the post-injury environment and to internal programs that govern growth. In previous work we have discovered that a small percentage of axons do re-grow in the adult CNS when presented with appropriate growth signals. Dr. Horner's lab is currently trying to understand the genetic programs that allow one subset of axons to re-grow in an injury environment while another cannot.

The goal of this study is to unlock the potential of the adult nervous system by stimulating cell replacement via endogenous stem cells and to promote axonal regeneration through gene therapy.

For more information, please visit: http://www.glaucoma.org/research/researchers.php

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Stem Cell-Derived Astrocytes as a Transplantable Resource for Spinal Cord Lesion Repair and Plasticity

Principal Investigator: Philip Horner, PhD
Funded By: Mike Utly Foundation

Astrocytes represent a morphologically and functionally diverse population of cells in the central nervous system (CNS). A particular subset of these cells, reactive astrocytes, forms in response to a number of CNS insults, including spinal cord injury. These cells are thought to provide an innate defense mechanism separating normal from damaged nervous tissue, thereby limiting the extent of injury. However, this occurs at the expense of axon regeneration and functional recovery. The heterogeneity of astrocytes with respect to differentiation pathways and ultimate functionality can be explored through the manipulation of endogenous neural progenitor cells (NPCs).

Whether or not different subtypes of astrocytes behave differently in the post-injury environment remains unclear. Work has already been initiated in murine models to investigate this effect, but its application in humans has yet to be explored. The recent achievement of generating induced pluripotent stem cells (iPS) from human fibroblasts has created a unique opportunity to investigate post-injury astrocyte behavior in a manner more directly applicable to humans. The goal of this research is to show that astrocytes can be generated from iPS cells through multiple signaling pathways (BMP4 or CNTF and LIF) and that they will differ both in vitro and in vivo with respect to their abilities to support axon regeneration.

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The Adult Neural Stem Cell and Spinal Cord Remodeling

Principal Investigator: Philip Horner, PhD
Funded By: Craig H Neilsen Foundation

A traumatic spinal cord injury (SCI) in adult mice initiates a series of events: the lesion epicenter is an open area to the immune cells and become a necrotic area surround by a glial scar (an area deprived of neuronal cells). It is accepted that glial scar is one impediment to regeneration after an SCI. Dr. Horner hypothesizes that repulsive cues at the injury site drive out endogenous or transplanted stem cells creating a void & scar. Studies indicate that adult neural stem cells are born within the lesion epicenter but are repulsed by: netrin-1.

Dr. Horner proposes that after a SCI, an increase in netrin-1 at the injury epicenter prevents the survival of stem cells. He proposes that down-regulation of netrin-1 after a SCI will allow survival of endogenous neural stem cell or grafted adult spinal cord progenitor cells (aSCP) to create a regenerative matrix. In this project, netrin-1 will be blocked by small interference RNAs (molecules that prevent netrin-1 protein formation) after a SCI. The study determine the effect on the ability of stem cells to migrate and remain within the lesion site and their ability to regenerate neural tissue. The study will also analyse the recovery of locomotor function using behavioural tests.

The experiments outlined are designed to better understand the ability of neural stem cells to respond to guidance cues previously studied during neural system development. If true, these studies would provide a road-map for unlocking the potential of stem cells to thrive and regenerate a lesion core following SCI.

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