Treatment of chronic thoracic spinal cord injury patients with autologous Schwann cell transplantation: An interim report on safety considerations and possible outcomes

Saberi, Hooshang; Moshayedi, Pouria; Aghayan, Hamid Reza; Arjmand, Babak; Hosseini, Seyed-Kazem; Emami-Razavi, Seyed-Hassan; Rahimi‐Movaghar, Vafa; Raza, Mohsin; Firouzi, Masoumeh

doi:10.1016/j.neulet.2008.07.041

Cited by 154 publications

(115 citation statements)

References 26 publications

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“…These behavioral findings suggest that additional, well-designed, and properly controlled studies are needed to assess the functional benefits of SCs. While the focus of interest is in the development of SCs as a transplantation therapy, as multiple centers move toward or have begun human clinical trails (Saberi et al, 2008), there is strong preclinical interest in the use of additional experimental cotreatments. However, translating such a combination of two experimental treatments into clinical trials has significant implications from a regulatory standpoint, particularly if each treatment in the ''co-treatment'' is experimental.…”

Section: Behaviormentioning

confidence: 99%

A Systematic Review of Cellular Transplantation Therapies for Spinal Cord Injury

Tetzlaff

Okon

Karimi-Abdolrezaee

et al. 2011

Journal of Neurotrauma

496

463

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Cell transplantation therapies have become a major focus in pre-clinical research as a promising strategy for the treatment of spinal cord injury (SCI). In this article, we systematically review the available pre-clinical literature on the most commonly used cell types in order to assess the body of evidence that may support their translation to human SCI patients. These cell types include Schwann cells, olfactory ensheathing glial cells, embryonic and adult neural stem=progenitor cells, fate-restricted neural=glial precursor cells, and bone-marrow stromal cells. Studies were included for review only if they described the transplantation of the cell substrate into an in-vivo model of traumatic SCI, induced either bluntly or sharply. Using these inclusion criteria, 162 studies were identified and reviewed in detail, emphasizing their behavioral effects (although not limiting the scope of the discussion to behavioral effects alone). Significant differences between cells of the same ''type'' exist based on the species and age of donor, as well as culture conditions and mode of delivery. Many of these studies used cell transplantations in combination with other strategies. The systematic review makes it very apparent that cells derived from rodent sources have been the most extensively studied, while only 19 studies reported the transplantation of human cells, nine of which utilized bone-marrow stromal cells. Similarly, the vast majority of studies have been conducted in rodent models of injury, and few studies have investigated cell transplantation in larger mammals or primates. With respect to the timing of intervention, nearly all of the studies reviewed were conducted with transplantations occurring subacutely and acutely, while chronic treatments were rare and often failed to yield functional benefits.

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Section: Behaviormentioning

confidence: 99%

A Systematic Review of Cellular Transplantation Therapies for Spinal Cord Injury

Tetzlaff

Okon

Karimi-Abdolrezaee

et al. 2011

Journal of Neurotrauma

496

463

View full text Add to dashboard Cite

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“…A n increasing number of cell-based therapies are moving towards human use for repair of spinal cord injury (SCI; Chernykh et al, 2007;Dobkin et al, 2006;Knoller et al, 2005;Mackay-Sim et al, 2008;Saberi et al, 2008;Tator, 2006;Yoon et al, 2007). One challenge that may limit their efficacy is the early death of transplanted cells.…”

Section: Introductionmentioning

confidence: 99%

A Calpain Inhibitor Enhances the Survival of Schwann CellsIn Vitroand after Transplantation into the Injured Spinal Cord

Hill

Guller

Raffa

et al. 2010

Journal of Neurotrauma

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Despite the diversity of cells available for transplantation into sites of spinal cord injury (SCI), and the known ability of transplanted cells to integrate into host tissue, functional improvement associated with cellular transplantation has been limited. One factor potentially limiting the efficacy of transplanted cells is poor cell survival. Recently we demonstrated rapid and early death of Schwann cells (SCs) within the first 24 h after transplantation, by both necrosis and apoptosis, which results in fewer than 20% of the cells surviving beyond 1 week. To enhance SC transplant survival, in vitro and in vivo models to rapidly screen compounds for their ability to promote SC survival are needed. The current study utilized in vitro models of apoptosis and necrosis, and based on withdrawal of serum and mitogens and the application of hydrogen peroxide, we screened several inhibitors of apoptosis and necrosis. Of the compounds tested, the calpain inhibitor MDL28170 enhanced SC survival both in vitro in response to oxidative stress induced by application of H 2 O 2 , and in vivo following delayed transplantation into the moderately contused spinal cord. The results support the use of calpain inhibitors as a promising new treatment for promoting the survival of transplanted cells. They also suggest that in vitro assays for cell survival may be useful for establishing new compounds that can then be tested in vivo for their ability to promote transplanted SC survival.

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“…In both studies, there were no significant changes in patients' MRI scans, and they reported neither neurological worsening nor improvement. They only reported autonomic functional recovery and improved quality of life 12,13 .…”

Section: Schwann Cellsmentioning

confidence: 99%

Current perspectives in stem cell therapy for spinal cord repair in humans: a review of work from the past 10 years

Mariano

Batista

Barbosa

et al. 2014

Arq. Neuro-Psiquiatr.

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Spinal cord injury (SCI) and amyotrophic laterals sclerosis (ALS) are devastating neurological conditions that affect individuals worldwide, significantly reducing quality of life, both for patients and their relatives. Objective: The present review aims to summarize the multiple restorative approaches being developed for spinal cord repair, the use of different stem cell types and the current knowledge regarding stem cell therapy. Method: Review of the literature from the past 10 years of human studies using stem cell transplantation as the main therapy, with or without adjuvant therapies. Conclusion: The current review offers an overview of the state of the art regarding spinal cord restoration, and serves as a starting point for future studies.Keywords: spinal cord injury, amyotrophic lateral sclerosis, stem cells, stem cell therapy. RESUMOLesão medular (LM) e esclerose lateral amiotrófica (ELA) são condições devastadoras que acometem pessoas em todo o mundo, reduzindo a qualidade de vida tanto de pacientes como de entes queridos. Objetivo: A atual revisão tem como alvo as múltiplas abordagens restauradoras para a regeneração medular, o uso de diferentes tipos celulares e o atual conhecimento a cerca da terapia com células tronco. Método: Revisão de literatura dos últimos 10 anos usando transplantes de células tronco como estratégia principal, com ou sem terapia adjuvante, em humanos. Conclusão: A presente revisão oferece uma visão geral acerca da restauração medular e serve de ponto de partida para estudos futuros.Palavras-chave: lesão medular, esclerose lateral amiotrófica, células tronco, terapia com células tronco.

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Treatment of chronic thoracic spinal cord injury patients with autologous Schwann cell transplantation: An interim report on safety considerations and possible outcomes

Cited by 154 publications

References 26 publications

A Systematic Review of Cellular Transplantation Therapies for Spinal Cord Injury

A Systematic Review of Cellular Transplantation Therapies for Spinal Cord Injury

A Calpain Inhibitor Enhances the Survival of Schwann CellsIn Vitroand after Transplantation into the Injured Spinal Cord

Current perspectives in stem cell therapy for spinal cord repair in humans: a review of work from the past 10 years

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