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

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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.

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Most cited references 31

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Lumbar intraspinal injection of neural stem cells in patients with amyotrophic lateral sclerosis: results of a phase I trial in 12 patients.

Seward B. Rutkove, Jonathan Glass, Meraida Polak … (2012)

Advances in stem cell biology have generated intense interest in the prospect of transplanting stem cells into the nervous system for the treatment of neurodegenerative diseases. Here, we report the results of an ongoing phase I trial of intraspinal injections of fetal-derived neural stems cells in patients with amyotrophic lateral sclerosis (ALS). This is a first-in-human clinical trial with the goal of assessing the safety and tolerability of the surgical procedure, the introduction of stem cells into the spinal cord, and the use of immunosuppressant drugs in this patient population. Twelve patients received either five unilateral or five bilateral (10 total) injections into the lumbar spinal cord at a dose of 100,000 cells per injection. All patients tolerated the treatment without any long-term complications related to either the surgical procedure or the implantation of stem cells. Clinical assessments ranging from 6 to 18 months after transplantation demonstrated no evidence of acceleration of disease progression due to the intervention. One patient has shown improvement in his clinical status, although these data must be interpreted with caution since this trial was neither designed nor powered to measure treatment efficacy. These results allow us to report success in achieving the phase I goal of demonstrating safety of this therapeutic approach. Based on these positive results, we can now advance this trial by testing intraspinal injections into the cervical spinal cord, with the goal of protecting motor neuron pools affecting respiratory function, which may prolong life for patients with ALS. Copyright © 2012 AlphaMed Press.

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Burden of spinal cord injury-related neuropathic pain in the United States: retrospective chart review and cross-sectional survey.

Richard Stacey, M Tuchman, Edward Nieshoff … (2013)

Cross-sectional, observational study. Characterize demographic and clinical characteristics, health status, pain, function, productivity and economic burden in spinal cord injury-related neuropathic pain (SCI-NeP) subjects, by pain severity. United States. One hundred and three subjects diagnosed with SCI-NeP recruited during routine primary care or specialty physician office visits completed a questionnaire to assess patient-reported outcomes. Physicians completed a case report form on inclusion/exclusion criteria, subject clinical characteristics and health-care resource use (HRU) based on 6-month retrospective chart review. Subjects' mean age was 48.7, 69.9% were male and 48.5% were unable to walk. The most frequently reported comorbidities were sleep disturbance/insomnia (28.2%), depressive symptoms (25.2%) and anxiety (23.3%). Subjects' mean pain severity score was 5.3 (0-10 scale), and 77.7% reported moderate or severe pain. On a 0-10 scale, subjects' reported moderate pain interference with function: mean 5.4. Subjects' health status, as measured by the EuroQol 5-dimensions health-state utility, was 0.49 (-0.11 to 1.00 scale). Pain interference with function and health status were significantly worse among subjects with more severe pain (P<0.0005). Among employed subjects (13.6%), overall work impairment was 38.0%. The proportion of subjects who were prescribed ≥1 medication was 94.2%, and the mean number of physician office visits in past 6 months due to SCI-NeP was 2.2. Total annualized cost per subject was $26 270 (direct: $8636, indirect: $17 634). SCI-NeP subjects exhibited high pain levels, despite active management. Pain levels were associated with poor function, low health status and lost productivity. HRU was prevalent, and costs, particularly indirect, were substantial, highlighting unmet need. This study was supported by Pfizer, Inc.

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Metal-related artifacts in instrumented spine. Techniques for reducing artifacts in CT and MRI: state of the art.

A Curti, P Stradiotti, A Zerbi … (2009)

The projectional nature of radiogram limits its amount of information about the instrumented spine. MRI and CT imaging can be more helpful, using cross-sectional view. However, the presence of metal-related artifacts at both conventional CT and MRI imaging can obscure relevant anatomy and disease. We reviewed the literature about overcoming artifacts from metallic orthopaedic implants at high-field strength MRI imaging and multi-detector CT. The evolution of multichannel CT has made available new techniques that can help minimizing the severe beam-hardening artifacts. The presence of artifacts at CT from metal hardware is related to image reconstruction algorithm (filter), tube current (in mA), X-ray kilovolt peak, pitch, hardware composition, geometry (shape), and location. MRI imaging has been used safely in patients with orthopaedic metallic implants because most of these implants do not have ferromagnetic properties and have been fixed into position. However, on MRI imaging metallic implants may produce geometric distortion, the so-called susceptibility artifact. In conclusion, although 140 kV and high milliamperage second exposures are recommended for imaging patients with hardware, caution should always be exercised, particularly in children, young adults, and patients undergoing multiple examinations. MRI artifacts can be minimized by positioning optimally and correctly the examined anatomy part with metallic implants in the magnet and by choosing fast spin-echo sequences, and in some cases also STIR sequences, with an anterior to posterior frequency-encoding direction and the smallest voxel size.

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Author and article information

Journal

Journal ID (nlm-ta): Curr Opin Organ Transplant

Journal ID (iso-abbrev): Curr Opin Organ Transplant

Journal ID (publisher-id): COOTR

Title: Current Opinion in Organ Transplantation

Publisher: Lippincott Williams & Wilkins

ISSN (Print): 1087-2418

ISSN (Electronic): 1531-7013

Publication date (Print): December 2013

Publication date (Electronic): 13 November 2013

Volume: 18

Issue: 6

Pages: 682-689

Affiliations

[a ]Department of Neurological Surgery

[b ]The Miami Project to Cure Paralysis, Lois Pope LIFE Centre, Miller School of Medicine, Miami, Florida, USA

Article

DOI: 10.1097/MOT.0000000000000026

PMC ID: 3864173

PubMed ID: 24220051

SO-VID: 2c210845-2b83-4124-964f-af4ab6d9678d

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This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

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Keywords: cell culture,autologous,transplant,spinal cord injury,schwann cell

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Keywords: cell culture, autologous, transplant, spinal cord injury, schwann cell

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

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Abstract

Purpose of review

Recent findings

Summary

Related collections

In vitro alveolar region models

Most cited references 31

Lumbar intraspinal injection of neural stem cells in patients with amyotrophic lateral sclerosis: results of a phase I trial in 12 patients.

Burden of spinal cord injury-related neuropathic pain in the United States: retrospective chart review and cross-sectional survey.

Metal-related artifacts in instrumented spine. Techniques for reducing artifacts in CT and MRI: state of the art.

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