Safety and neurological assessments after autologous transplantation of bone marrow mesenchymal stem cells in subjects with chronic spinal cord injury.

Marcus Vinícius Pinheiro Mendonça,Geraldo Pedral Sampaio,Sissi Brandão Carneiro Furtado,Bruno Solano De Freitas Souza,Carla Martins Kaneto,Ana Carine De Oliveira Melo Martinez,Ricardo Ribeiro Dos Santos,André Costa Matos,Ticiana Ferreira Larocca,Cláudia Maria Pinheiro Bahia,Marco Antonio Novaes,Cristiane Flora Villarreal,Milena Botelho Pereira Soares,Luiz Flávio Maia Silva

doi:10.1186/scrt516

Abstract

IntroductionThe administration of stem cells holds promise as a potential therapy for spinal cord injury (SCI). Mesenchymal stem cells have advantages for clinical applications, since they can be easily obtained, are suitable for autologous transplantation and have been previously shown to induce regeneration of the spinal cord in experimental settings. Here we evaluated the feasibility, safety and potential efficacy of autologous transplantation of mesenchymal stem cells in subjects with chronic complete SCI.MethodWe conducted a phase I, non-controlled study in 14 subjects of both genders aging between 18 to 65 years, with chronic traumatic SCI (>6 months), at thoracic or lumbar levels, classified as American Spinal Injury Association (ASIA) A - complete injury. Baseline somatosensory evoked potentials (SSEP), spinal magnetic resonance imaging (MRI) and urodynamics were assessed before and after treatment. Pain rating was performed using the McGill Pain Questionnaire and a visual analogue score scale. Bone marrow-derived mesenchymal stem cells were cultured and characterized by flow cytometry, cell differentiation assays and G-band karyotyping. Mesenchymal stem cells were injected directly into the lesion following laminectomy and durotomy.ResultsCell transplantation was an overall safe and well-tolerated procedure. All subjects displayed variable improvements in tactile sensitivity and eight subjects developed lower limbs motor functional gains, principally in the hip flexors. Seven subjects presented sacral sparing and improved American Spinal Injury Association impairment scale (AIS) grades to B or C – incomplete injury. Nine subjects had improvements in urologic function. One subject presented changes in SSEP 3 and 6 months after mesenchymal stem cells transplantation. Statistically significant correlations between the improvements in neurological function and both injury size and level were found.ConclusionIntralesional transplantation of autologous mesenchymal stem cells in subjects with chronic, complete spinal cord injury is safe, feasible, and may promote neurological improvements.Trial registrationClinicalTrials.gov NCT01325103 – Registered 28 March 2011

Highlights

The administration of stem cells holds promise as a potential therapy for spinal cord injury (SCI)
The main objective was to evaluate the safety of autologous bone marrow mesenchymal stem cell (MSC) transplantation in subjects with chronic traumatic SCI
Fourteen subjects were assigned to the study condition and were submitted to bone marrow aspiration and MSC transplantation

Summary

Introduction

The administration of stem cells holds promise as a potential therapy for spinal cord injury (SCI). Several studies have indicated a beneficial role for transplantation of different cell types, including bone marrow cells, neural progenitor cells and olfactory ensheathing cells, into the injured spinal cord [2,3,4,5,6]. Another approach that has been tested is the use of oligodendrocyte progenitor cells to promote oligodendrogenesis after SCI, which led to remyelinization and motor function improvement [7]

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