Neuroprotection and Axonal Regeneration After Lumbar Ventral Root Avulsion by Re-implantation and Mesenchymal Stem Cells

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ORIGINAL ARTICLE

Neuroprotection and Axonal Regeneration After Lumbar Ventral Root Avulsion by Re-implantation and Mesenchymal Stem Cells Transplant Combined Therapy Abel Torres-Espín & Dora Luz Corona-Quintanilla & Joaquim Forés & Ilary Allodi & Francisco González & Esther Udina & Xavier Navarro

Published online: 26 February 2013 # The American Society for Experimental NeuroTherapeutics, Inc. 2013

Abstract Ventral spinal root avulsion causes complete denervation of muscles in the limb and also progressive death of segmental motoneurons (MN) leading to permanent paralysis. The chances for functional recovery after ventral root avulsion are very poor owing to the loss of avulsed neurons and the long distance that surviving neurons have to re-grow axons from the spinal cord to the corresponding targets. Following unilateral avulsion of L4, L5 and L6 spinal roots in adult rats, we performed an intraspinal transplant of mesenchymal stem cells (MSC) and surgical re-implantation of the avulsed roots. Four weeks after avulsion the survival of MN in the MSC-treated animals was significantly higher than in vehicle-injected rats (45 % vs 28 %). Re-implantation of the avulsed roots in the injured spinal cord allowed the regeneration of motor axons. By combining root re-implantation and MSC transplant the

number of surviving MN at 28 days post-injury was higher (60 %) than in re-implantation alone animals (46 %). Electromyographic tests showed evidence of functional re-innervation of anterior tibialis and gastrocnemius muscles by the regenerated motor axons only in rats with the combined treatment. These results indicate that MSC are helpful in enhancing neuronal survival and increased the regenerative growth of injured axons. Surgical re-implantation and MSC grafting combined had a synergic neuroprotective effect on MN and on axonal regeneration and muscle re-innervation after spinal root avulsion.

Electronic supplementary material The online version of this article (doi:10.1007/s13311-013-0178-5) contains supplementary material, which is available to authorized users.

Introduction

A. Torres-Espín : D. L. Corona-Quintanilla : I. Allodi : F. González : E. Udina : X. Navarro Group of Neuroplasticity and Regeneration, Institute of Neurosciences, Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain D. L. Corona-Quintanilla Centro Tlaxcala de Biología de la Conducta, Universidad Autónoma de Tlaxcala, Tlaxcala, Mexico J. Forés Hand and Peripheral Nerve Unit, Hospital Clínic i Provincial, Universitat de Barcelona, Barcelona, Spain X. Navarro (*) Unitat de Fisiologia Mèdica, Edif. M, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Spain e-mail: [email protected]

Keywords Ventral root . Motoneuron . Neuroprotection . Axonal regeneration . Stem cells . Surgical repair

Avulsion of the spinal roots causes disconnection between the peripheral and the central nervous system