Dataset Information

Clinical translation of autologous Schwann cell transplantation for the treatment of spinal cord injury.

ABSTRACT:

Purpose of review

To describe the current status of testing Schwann cell transplantation as a therapy for human spinal cord injury (SCI).

Recent findings

Transplanted Schwann cells have reparative effects in the damaged spinal cord. A few clinical studies have reported that Schwann cell transplantation appears safe. Compared with allogeneic cell transplants, autologous cells do not require immune suppression, but the workload of cell manufacturing is greater. Preclinical Schwann cell transplant studies conducted at the University of Miami in 2009-2012 supported an investigational new drug approved by the Food and Drug Administration. A Phase 1 safety study has been initiated.

Summary

Spinal cord repair after severe SCI requires that axonal regeneration and myelination occur in a context of reduced inhibition, enhanced plasticity, and new circuit formation. Evolving clinical experience with Schwann cell transplantation may provide a basis upon which additionally combined therapeutics can be tested to increase the extent of repair after SCI. Safety is the primary consideration when ex-vivo manipulated cells are introduced into the damaged nervous system. Preclinical studies across several species have not indicated safety concerns regarding Schwann cells. Initial clinical reports from studies in Iran and China are suggestive of clinical safety, although more rigorous characterization of the implanted cells is needed.

SUBMITTER: Guest J

PROVIDER: S-EPMC3864173 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The transplantation of Schwann cells (SCs) has been shown to provide tissue preservation and support axon growth and remyelination as well as improve functional recovery across a diverse range of experimental spinal cord injury (SCI) paradigms. The autologous use of SCs has progressed to Phase 1 SCI clinical trials in humans where their use has been shown to be both feasible and safe. The contribution of immune modulation to the protective and reparative actions of SCs within the injured spinal cord remains largely unknown. In the current investigation, the ability of SC transplants to alter the innate immune response after contusive SCI in the rat was examined. SCs were intraspinally transplanted into the lesion site at 1 week following a thoracic (T8) contusive SCI. Multicolor flow cytometry and immunohistochemical analysis of specific phenotypic markers of pro- and anti-inflammatory microglia and macrophages as well as cytokines at 1 week after SC transplantation was employed. The introduction of SCs significantly attenuated the numbers of cluster of differentiation molecule 11B (CD11b)?, cluster of differentiation molecule 68 (CD68)?, and ionized calcium-binding adapter molecule 1 (Iba1)? immune cells within the lesion implant site, particularly those immunoreactive for the pro-inflammatory marker, inducible nitric oxide synthase (iNOS). Whereas numbers of anti-inflammatory CD68? Arginase-1 (Arg1?) iNOS- cells were not altered by SC transplantation, CD68? cells of an intermediate, Arg1? iNOS? phenotype were increased by the introduction of SCs into the injured spinal cord. The morphology of Iba1? immune cells was also markedly altered in the SC implant, being elongated and in alignment with SCs and in-growing axons versus their amoeboid form after SCI alone. Examination of pro-inflammatory cytokines, tumor necrosis factor-? (TNF-?) and interleukin-1? (IL-1?), and anti-inflammatory cytokines, interleukin-4 (IL-4) and interleukin-10 (IL-10), by multicolor flow cytometry analysis showed that their production in CD11b? cells was unaltered by SC transplantation at 1 week post-transplantation. The ability of SCs to subdue the pro-inflammatory iNOS? microglia and macrophage phenotype after intraspinal transplantation may provide an important contribution to the neuroprotective effects of SCs within the sub-acute SCI setting.