Repair of the injured spinal cord and the potential of embryonic stem cell transplantation.
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.
McDonald
John W
JW
Department of Neurology and Neurological Surgery, Washington University School of Medicine, St Louis, Missouri, USA.
Becker
Daniel
D
Holekamp
Terrence F
TF
Howard
Michael
M
Liu
Su
S
Lu
Aiwu
A
Lu
James
J
Platik
Marina M
MM
Qu
Yun
Y
Stewart
Todd
T
Vadivelu
Sudhakar
S
D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D009416:Nerve Regeneration / Q000235:genetics*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods / Q000639:trends*
D015415:Biomarkers