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R. Mark Richardson, Helen L. Fillmore, Kathryn L. Holloway and William C. Broaddus

stem cells being developed to treat pathological conditions of the brain raise important questions concerning the practical differences between primary tissue grafts and cells expanded in vitro before transplantation, which are relevant to the use of cells in restorative neurosurgery. In preparation for the eventual availability of multiple types of expanded stem cells for use in transplantation, the neurosurgical community should be aware that NSCs expanded from diverse tissues, developmental stages, and species have exhibited important functional distinctions as

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Christopher Thomas Scott

L ast November's discoveries of iSPC lines made without embryos provoked much publicity and renewed the debate about whether these cells will eliminate the need to use pluripotent stem cells made from leftover human embryos. These questions will be answered with time and more research, and the new cells may join adult and ESC lines already in the laboratory and on the road to the clinic. As the debate about the human embryo continues to simmer, the science has moved ahead. So too has the study of the ethical, legal, and policy dimensions of stem cell

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Sudhakar Vadivelu, Matthew Willsey, Daniel J. Curry and John W. McDonald III

strategies. Intractable neuropathic pain has gained increasing awareness due to its prevalence and the technological advancements in surgical neuromodulation. Electrical stimulation via spinal cord, peripheral nerve, and deep brain targeting has begun to show some early efficacy. 18 To date, chronic neuropathic pain is largely considered a heterogeneous pain syndrome that remains with limited efficacious treatment modalities. Also, there is no treatment strategy that is effective for pain management while promoting nervous system repair. Stem cell transplantation is a

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Rahul Jandial, Henry E. Aryan, John Park, William T. Taylor and Evan Y. Snyder

T he discovery of stem cells has provided tremendous momentum to the field of regenerative medicine, and the therapeutic potential of stem cells in the treatment of IVD disease is generating significant clinical interest. Given the numerous patients afflicted with back pain and disc degeneration, along with the advances in minimally invasive spine surgery, the marriage between surgery and cell transplantation could yield significant improvements to the currently limited tools for treating disc disease. The physiological environment of the IVD is largely

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Michael C. Jin, Zachary A. Medress, Tej D. Azad, Vanessa M. Doulames and Anand Veeravagu

phases. Primary injury refers to the initial shearing or compression of the spinal cord tissue. The mechanical force of the primary injury causes hemorrhage, disruption of cell membrane integrity, and ion and neurotransmitter imbalance that immediately compromises neural function. Secondary injury pertains to the progressive inflammatory, ischemic, and apoptotic cascade that follows the initial mechanical assault. 52 Stem cell therapies for SCI seek to minimize the spread of secondary injury, augment the function of remaining cell populations, and facilitate

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Stem cell studies of human malignant brain tumors

Part 1: Development of the stem cell assay and its potential

Mark L. Rosenblum, Massimo A. Gerosa, Charles B. Wilson, Geoffrey R. Barger, Bertran F. Pertuiset, Nicolas de Tribolet and Dolores V. Dougherty

T he inexorable growth of a malignant tumor reflects multiplication of clonogenic tumor cells (“stemcells) with potential for “unlimited” proliferation. The number and type of these cells within a solid tumor, the kinetics of their growth, and their differential sensitivity to cytotoxic agents probably account for variations in tumor growth and responsiveness, described even among tumors of similar histology. In vitro assays of colony-forming cells have gained acceptance as a method for analysis of the clonogenic cell population. 5, 9, 22, 24 In vitro

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Hormoz Sheikh, Karen Zakharian, Ramiro Perez De La Torre, Christopher Facek, Adrian Vasquez, G. Rasul Chaudhry, David Svinarich and Mick J. Perez-Cruet

within the NP is largely unknown. It is believed that these cells also produce the proteoglycan matrix that holds the water molecules that maintain the viable function of the intervertebral disc. 1 , 12 , 21 The notochordal cells may represent a stem cell population within the NP, much like the mesenchymal cells within the bone marrow. Human as well as animal studies have shown that with age, the notochordal cell population disappears. 2 , 11 It is believed that as notochordal cells age, they may terminally differentiate into chondrocytes within the NP in older

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Nicholas C. Bambakidis, John Butler, Eric M. Horn, Xukui Wang, Mark C. Preul, Nicholas Theodore, Robert F. Spetzler and Volker K. H. Sonntag

injury cascade (neuroprotection), and those that target re-myelination and axonal and neuronal regeneration (neuroregeneration). To date, most work on the potential benefits of stem cell therapy in treating SCI has concentrated on neuroregeneration, the focus of this article. F ig . 1. Outline of the primary and secondary injury cascades after acute traumatic SCI. Originally published in Horn EM, Forage J, Sonntag VKH: Acute treatment of patients with spinal cord injuries, in Herkowitz HN, Gorfin SR, Eismont FJ, et al (eds): Rothman-Simeone the Spine, ed 5

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Moneeb Ehtesham, Charles B. Stevenson and Reid C. Thompson

The prognosis for patients with malignant glioma, which is the most common primary intracranial neoplasm, remains dismal despite significant progress in neurooncological therapies and technology. This is largely due to the inability of current treatment strategies to address the highly invasive nature of this disease. Malignant glial cells often disseminate throughout the brain, making it exceedingly difficult to target and treat all intracranial neoplastic foci, with the result that tumor recurrence is inevitable despite aggressive surgery and adjuvant radiotherapy and/or chemotherapy. The use of neural stem cells (NSCs) as delivery vehicles for tumor-toxic molecules represents the first experimental strategy aimed specifically at targeting disseminated tumor pockets. Investigators have demonstrated that NSCs possess robust tropism for infiltrating tumor cells, and that they can be used to deliver therapeutic agents directly to tumor satellites, with significant therapeutic benefit. With the aim of developing these findings into a clinically viable technology that would not be hindered by ethical and tissue rejection–related concerns, the use of adult tissue–derived stem cells has recently been explored. These technologies represent important progress in the development of a treatment strategy that can specifically target disseminated neoplastic pockets within the brain. Despite encouraging results in preclinical models, however, there are significant impediments that must be overcome prior to clinical implementation of this strategy. Key among these are an inadequate understanding of the specific tropic mechanisms that govern NSC migration toward invasive tumor, and the need to refine the processes used to generate tumor-tropic stem cells from adult tissues so that this can be accomplished in a clinically practicable fashion. Despite these limitations, the use of stem cell therapies for brain tumors holds significant promise and may emerge as an important therapeutic modality for patients with malignant glioma.

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Jae-Hoon Lee, Hwa-Seok Chang, Eun-Hee Kang, Dai-Jung Chung, Chi-Bong Choi, Jong-Hwan Lee, Soo-Han Hwang, Hoon Han and Hwi-Yool Kim

M any strategies for the treatment of traumatic SCI are focused on cellular therapies that promote remyelination and functional neurological recovery. These cellular therapies have entailed, at various times, the transplantation of bone marrow stromal cells, 3 , 30 human embryonic stem cell–derived oligodendrocyte progenitor cells, 16 hematopoietic stem cells from bone marrow, 18 and neural precursor cells. 15 Embryonic stem cell therapy can reduce behavioral defects in damaged and compromised spinal cords in animals and humans. However, embryonic stem