Demyelination contributes to the loss of function consequent to central nervous system (CNS) injury. Enhanced remyelination through transplantation of myelin-producing cells may offer a pragmatic approach to restoring meaningful neurological function. An unlimited source of cells suitable for such transplantation therapy can be derived from embryonic stem (ES) cells, which are both pluripotent and genetically flexible. In this paper we show that oligodendrocyte cultures can be reliably produced from retinoic acid-induced ES cells and that these oligodendrocytes can myelinate axons in vitro. Methods were further developed for generating highly enriched cultures of oligodendrocytes through an additional culturing step, producing an intermediate ''oligosphere'' stage. To test whether ES cells can survive, migrate, and differentiate into mature myelin-producing cells in areas of demyelination in the adult CNS, ES cells were transplanted into the dorsal columns of adult rat spinal cord 3 days after chemical demyelination. In the demyelination site, large numbers of ES cells survived and differentiated primarily into mature oligodendrocytes that were capable of myelinating axons. Furthermore, when oligosphere cells were transplanted into the spinal cords of myelindeficient shiverer (shi/shi) mutant mice, the ES cell-derived oligodendrocytes migrated into the host tissue, produced myelin and myelinated host axons. These studies demonstrate the ability of ES cell-derived oligodendrocytes to myelinate axons in culture and to replace lost myelin in the injured adult CNS. Transplantation of ES cells may be a practical approach to treatment of primary and secondary demyelinating diseases in the adult CNS. R ecovery in central nervous system (CNS) disorders is hindered by the limited ability of the vertebrate CNS to regenerate lost cells, replace damaged myelin, and re-establish functional neural connections. In many CNS disorders, including multiple sclerosis, stroke, spinal cord injury, and other trauma, demyelination of intact axons (1-4) is an important factor contributing to loss of function. Previous studies suggest that substantial recovery of function might be achieved through remyelination of otherwise intact axons (5). As a therapeutic modality, functional recovery through remyelination may prove to be a pragmatic approach to regeneration.Ethical considerations and a lack of a reliable source for undifferentiated pluripotent cells have limited the application of neural transplantation studies in humans. Embryonic stem cells (ES cells) provide a partial solution to these problems because they are genetically normal, pluripotent, capable of indefinite replication (6), and have been derived from several vertebrate species including mice (7,8) The purpose of the present studies was threefold: (i) to develop methods for producing enriched cultures of ES cell-derived oligodendrocytes, (ii) to determine whether these cells could myelinate axons in vitro, and (iii) to determine whether ES cells would survive transplantati...

Subaxial cervical deformities most often occur in the sagittal plane, primarily as kyphosis. Kyphosis may develop secondary to advanced degenerative disease, trauma, neoplastic disease, or after surgery. Whatever the cause, the development of cervical deformity should be avoided and corrected when appropriate because the greater the deformity, the greater the probability of an associated neurological deficit or chronic pain. Patients usually present with mechanical type cervical pain, with or without neurological deficit (i.e., myelopathy). They may also be relatively asymptomatic. Work-up includes appropriate imaging studies, such as radiographs, including dynamic images, and magnetic resonance imaging or computed tomography myelography. The deformity may be accurately assessed and an appropriate surgical strategy undertaken. Depending on flexibility of the deformity and the presence or absence of facet ankylosis, a dorsal, ventral, or combined approach may be used. All approaches are unique in their ability to correct a deformity and in their associated complications. A comprehensive discussion of each is undertaken.

Revision spinal surgery is usually indicated in cases of persistent or recurrent symptoms related to neural compression, spinal deformity, or construct failure. An understanding of fundamental biomechanical principles of both spinal decompression and reconstructive strategies is essential to avoid unnecessary subsequent spinal operations.

Cervical spondylotic myelopathy (CSM) refers to impaired function of the spinal cord caused by degenerative changes of the cervical spine resulting in spinal cord compression. It is the most common disorder in the United States causing dysfunction of the spinal cord. A literature review of the natural history of mild cervical myelopathy is undertaken. Clinical presentation and current concepts of pathophysiology are also discussed. While many patients with mild signs of CSM will stabilize or improve over time with conservative treatment, the clinical course of a specific individual patient cannot be predicted. Asymptomatic patients with cervical stenosis and abnormalities on electrophysiologic studies may be at higher risk for developing myelopathy.

Traditionally, treatment of spinal cord injury seemed frustrating and hopeless because of the remarkable morbidity and mortality, and restricted therapeutic options. Recent advances in neural injury and repair, and the progress towards development of neuroprotective and regenerative interventions are basis for increased optimism. Neural stem cells have opened a new arena of discovery for the field of regenerative science and medicine. Embryonic stem (ES) cells can give rise to all neural progenitors and they represent an important scientific tool for approaching neural repair. The growing number of dedicated regeneration centers worldwide exemplifies the changing perception towards the do-ability of spinal cord repair and this review was born from a presentation at one such leading center, the Kentucky Spinal Cord Injury Research Center. Current concepts of the pathophysiology, repair, and restoration of function in the damaged spinal cord are presented with an overlay of how neural stem cells, particularly ES cells, fit into the picture as important scientific tools and therapeutic targets. We focus on the use of genetically tagged and selectable ES cell lines for neural induction and transplantation. Unique features of ES cells, including indefinite replication, pluripotency, and genetic flexibility, provide strong tools to address questions of neural repair. Selective marker expression in transplanted ES cell derived neural cells is providing new insights into transplantation and repair not possible previously. These features of ES cells will produce a predictable and explosive growth in scientific tools that will translate into discoveries and rapid progress in neural repair.

The ventrolateral approach for surgical decompression of the cervical spine is widely used and well known to most spinal surgeons. Because compression of the spinal cord and nerve roots usually occurs ventral to the spinal cord, and the spinal cord does not tolerate traction, this approach allows safe and direct decompression of most compressive pathology. This article reviews the indications, diagnostic evaluation, and technique for multiple level discectomy and fusion. It further addresses the advantages and disadvantages of this technique compared with alternate surgical procedures.

The glial scar resulting from spinal cord injury is rich in chondroitin sulfate proteoglycan (CSPG), a formidable barrier to axonal regeneration. We explored the possibility of breaching that barrier by first examining the scar in a functional in vitro model. We found that embryonic stem cell-derived neural lineage cells (ESNLCs) with prominent expression of nerve glial antigen 2 (NG2) survived, passed through an increasingly inhibitory gradient of CSPG, and expressed matrix metalloproteinase 9 (MMP-9) at the appropriate stage of their development. Outgrowth of axons from ESNLCs followed because the migrating cells sculpted pathways in which CSPG was degraded. The degradative mechanism involved MMP-9 but not MMP-2. To confirm these results in vivo, we transplanted ESNLCs directly into the cavity of a contused spinal cord 9 days after injury. A week later, ESNLCs survived and were expressing both NG2 and MMP-9. Their axons had grown through long distances (>10 mm), although they preferred to traverse white rather than gray matter. These data are consistent with the concept that expression of inhibitory CSPG within the injury scar is an important impediment to regeneration but that NG2+ progenitors derived from ESNLCs can modify the microenvironment to allow axons to grow through the barrier. This beneficial action may be partly due to developmental expression of MMP-9. We conclude that it might eventually be possible to encourage axonal regeneration in the human spinal cord by transplanting ESNLCs or other cells that express NG2. STEM CELLS

Progressive kyphotic deformity of the cervical spine may be a late sequela of congenital cervical anomalies, degenerative disc disease, neoplasm, cervical trauma, and surgical procedures. Of these, postsurgical kyphosis is the most common and can occur after ventral and dorsal surgeries of the cervical spine. The purpose of this article is to review the causes and clinical presentation of postsurgical cervical kyphosis and to focus on the operative planning and ventral correction techniques.