Hepatocyte Growth Factor-Preconditioned Neural Progenitor Cells Attenuate Astrocyte Reactivity and Promote Neurite Outgrowth.

The astroglial scar is a defining hallmark of secondary pathology following central nervous system (CNS) injury that, despite its role in limiting tissue damage, presents a significant barrier to neuroregeneration. Neural progenitor cell (NPC) therapies for tissue repair and regeneration have demonstrated favorable outcomes, the effects of which are ascribed not only to direct cell replacement but trophic support. Cytokines and growth factors secreted by NPCs aid in modifying the inhibitory and cytotoxic post-injury microenvironment.

Navigating the Postgraduate Research Fellowship: A Roadmap for Surgical Residents.

Background: To preserve the future of surgical innovation, opportunities for surgical residents to receive structured research training are paramount. The objective of this article is to help surgical residents navigate a research fellowship by overviewing key topics such as choosing an area of focus and supervisor, applying for external funding, transitioning away from clinical duties, managing intellectual property, integrating family planning, and incorporating research experience into independent career development.

Materials And Methods: Using the framework of the University of Toronto's graduate degree-awarding Surgeon-Scientist Training Program, the authors outline key considerations, decisions, and pearls for surgical residents considering or currently enrolled in a full-time research fellowship training program.

The leading edge: Emerging neuroprotective and neuroregenerative cell-based therapies for spinal cord injury.

Spinal cord injuries (SCIs) are associated with tremendous physical, social, and financial costs for millions of individuals and families worldwide. Rapid delivery of specialized medical and surgical care has reduced mortality; however, long-term functional recovery remains limited. Cell-based therapies represent an exciting neuroprotective and neuroregenerative strategy for SCI.

Degenerative cervical myelopathy - update and future directions.

Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord dysfunction in adults worldwide. DCM encompasses various acquired (age-related) and congenital pathologies related to degeneration of the cervical spinal column, including hypertrophy and/or calcification of the ligaments, intervertebral discs and osseous tissues. These pathologies narrow the spinal canal, leading to chronic spinal cord compression and disability.

GDNF rescues the fate of neural progenitor grafts by attenuating Notch signals in the injured spinal cord in rodents.

Neural progenitor cell (NPC) transplantation is a promising strategy for the treatment of spinal cord injury (SCI). In this study, we show that injury-induced Notch activation in the spinal cord microenvironment biases the fate of transplanted NPCs toward astrocytes in rodents. In a screen for potential clinically relevant factors to modulate Notch signaling, we identified glial cell-derived neurotrophic factor (GDNF).

A Systematic Review of Definitions for Neurological Complications and Disease Progression in Patients Treated Surgically for Degenerative Cervical Myelopathy.

Study Design: Systematic review.

Objective: This review aims to (1) outline how neurological complications and disease progression are defined in the literature and (2) evaluate the quality of definitions using a novel four-point rating system.

Summary Of Background Data: Degenerative cervical myelopathy (DCM) is a progressive, degenerative spine disease that is often treated surgically.

Arachnoiditis Ossificans: A Rare Etiology of Oil-Based Spinal Myelography and Review of the Literature.

Background: Arachnoiditis ossificans (AO) is a rare entity characterized by the presence of calcified plaques formed by the metaplasia of arachnoid cells. Over 50 cases of AO have been reported, with predisposing factors including spinal trauma, hemorrhage, vascular abnormalities, and infection. The administration of oil-based contrast during myelography as an independent risk factor or in conjunction with other spinal pathology has been described in 9 cases.

Generation of Definitive Neural Progenitor Cells from Human Pluripotent Stem Cells for Transplantation into Spinal Cord Injury.

In this chapter, we first describe two interchangeable protocols optimized in our lab for deriving definitive neuronal progenitor cells from human pluripotent stem cells (hPSCs). The resultant NPCs can then be propagated and differentiated to produce differing proportions of neurons, oligodendrocytes, and astrocytes as required for in vitro cell culture studies or in vivo transplantation. Following these protocols, we explain the method for transplanting these cells into the rat model of spinal cord injury (SCI).

Time is spine: a review of translational advances in spinal cord injury.

Acute traumatic spinal cord injury (SCI) is a devastating event with far-reaching physical, emotional, and economic consequences for patients, families, and society at large. Timely delivery of specialized care has reduced mortality; however, long-term neurological recovery continues to be limited. In recent years, a number of exciting neuroprotective and regenerative strategies have emerged and have come under active investigation in clinical trials, and several more are coming down the translational pipeline.

Human Oligodendrogenic Neural Progenitor Cells Delivered with Chondroitinase ABC Facilitate Functional Repair of Chronic Spinal Cord Injury.

Treatment of chronic spinal cord injury (SCI) is challenging due to cell loss, cyst formation, and the glial scar. Previously, we reported on the therapeutic potential of a neural progenitor cell (NPC) and chondroitinase ABC (ChABC) combinatorial therapy for chronic SCI. However, the source of NPCs and delivery system required for ChABC remained barriers to clinical application.

Human Spinal Oligodendrogenic Neural Progenitor Cells Promote Functional Recovery After Spinal Cord Injury by Axonal Remyelination and Tissue Sparing.

Cell transplantation therapy utilizing neural precursor cells (NPCs) is a conceptually attractive strategy for traumatic spinal cord injury (SCI) to replace lost cells, remyelinate denuded host axons and promote tissue sparing. However, the number of mature oligodendrocytes that differentiate from typical NPCs remains limited. Herein, we describe a novel approach to bias the differentiation of directly reprogrammed human NPCs (drNPCs) toward a more oligodendrogenic fate (oNPCs) while preserving their tripotency.

Spinal Cord Injury-What Are the Controversies?

Traumatic spinal cord injuries have a tremendous impact on individuals, families, and society as a whole. Substantial heterogeneity in the patient population, their presentation and underlying pathophysiology has sparked debates along the care spectrum from initial assessment to definitive treatment. This article reviews spinal cord injury (SCI) management followed by a discussion of the salient controversies in the field.

Generation of Oligodendrogenic Spinal Neural Progenitor Cells From Human Induced Pluripotent Stem Cells.

This unit describes protocols for the efficient generation of oligodendrogenic neural progenitor cells (o-NPCs) from human induced pluripotent stem cells (hiPSCs). Specifically, detailed methods are provided for the maintenance and differentiation of hiPSCs, human induced pluripotent stem cell-derived neural progenitor cells (hiPS-NPCs), and human induced pluripotent stem cell-oligodendrogenic neural progenitor cells (hiPSC-o-NPCs) with the final products being suitable for in vitro experimentation or in vivo transplantation. Throughout, cell exposure to growth factors and patterning morphogens has been optimized for both concentration and timing, based on the literature and empirical experience, resulting in a robust and highly efficient protocol.

Neural stem cell mediated recovery is enhanced by Chondroitinase ABC pretreatment in chronic cervical spinal cord injury.

Traumatic spinal cord injuries (SCIs) affect millions of people worldwide; the majority of whom are in the chronic phase of their injury. Unfortunately, most current treatments target the acute/subacute injury phase as the microenvironment of chronically injured cord consists of a well-established glial scar with inhibitory chondroitin sulfate proteoglycans (CSPGs) which acts as a potent barrier to regeneration. It has been shown that CSPGs can be degraded in vivo by intrathecal Chondroitinase ABC (ChABC) to produce a more permissive environment for regeneration by endogenous cells or transplanted neural stem cells (NSCs) in the subacute phase of injury.

Assessment and management of acute spinal cord injury: From point of injury to rehabilitation.

Context: Spinal cord injury (SCI) is a devastating condition that can lead to significant neurological impairment and reduced quality of life. Despite advancements in our understanding of the pathophysiology and secondary injury mechanisms involved in SCI, there are currently very few effective treatments for this condition. The field, however, is rapidly changing as new treatments are developed and key discoveries are made.

Traumatic spinal cord injury.

Traumatic spinal cord injury (SCI) has devastating consequences for the physical, social and vocational well-being of patients. The demographic of SCIs is shifting such that an increasing proportion of older individuals are being affected. Pathophysiologically, the initial mechanical trauma (the primary injury) permeabilizes neurons and glia and initiates a secondary injury cascade that leads to progressive cell death and spinal cord damage over the subsequent weeks.

Future Advances in Spine Surgery: The AOSpine North America Perspective.

This focus issue highlights state-of-the-art techniques, equipment, and practices in the modern era of spine surgery while providing a glimpse into the next generation of patient care. A broad range of topics are presented to cover the full spectrum of the field. Degenerative diseases are discussed in a series of 3 articles on (1) pathophysiology, management, and surgical approaches to degenerative cervical myelopathy; (2) novel approaches to degenerative thoracolumbar disease (eg, interspinous process spacers, minimally invasive/endoscopic approaches); and (3) animal models and emerging therapeutics in degenerative disk disease.

Traumatic Spinal Cord Injury-Repair and Regeneration.

Background: Traumatic spinal cord injuries (SCI) have devastating consequences for the physical, financial, and psychosocial well-being of patients and their caregivers. Expediently delivering interventions during the early postinjury period can have a tremendous impact on long-term functional recovery.

Pathophysiology: This is largely due to the unique pathophysiology of SCI where the initial traumatic insult (primary injury) is followed by a progressive secondary injury cascade characterized by ischemia, proapoptotic signaling, and peripheral inflammatory cell infiltration.

Induced Pluripotent Stem Cells for Traumatic Spinal Cord Injury.

Spinal cord injury (SCI) is a common cause of mortality and neurological morbidity. Although progress had been made in the last decades in medical, surgical, and rehabilitation treatments for SCI, the outcomes of these approaches are not yet ideal. The use of cell transplantation as a therapeutic strategy for the treatment of SCI is very promising.

History of neurosurgery at University of Toronto: the St. Michael's story.

In this paper, the authors describe the history of neurosurgery at St. Michael's Hospital, University of Toronto. St.