Neuroprotection and immunomodulation by xenografted human mesenchymal stem cells following spinal cord ventral root avulsion.

Thiago B Ribeiro,Alessandro S Farias,Adriana S S Duarte,Fernando Pradella,Ana Leda F Longhini,Sara Teresinha Olalla Saad,Angela C M Luzo,Alexandre L R Oliveira

doi:10.1038/srep16167

Thiago B Ribeiro, Alessandro S Farias + Show 6 more

Open Access

https://doi.org/10.1038/srep16167

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Journal: Scientific reports	Publication Date: Nov 9, 2015
Citations: 54	License type: CC BY 4.0

Affiliation: Universidade Estadual de Campinas

Abstract

The present study investigates the effects of xenotransplantation of Adipose Tissue Mesenchymal Stem Cells (AT-MSCs) in animals after ventral root avulsion. AT-MSC has similar characteristics to bone marrow mesenchymal stem cells (BM-MSCs), such as immunomodulatory properties and expression of neurotrophic factors. In this study, Lewis rats were submitted to surgery for unilateral avulsion of the lumbar ventral roots and received 5 × 105 AT-MSCs via the lateral funiculus. Two weeks after cell administration, the animals were sacrificed and the moto neurons, T lymphocytes and cell defense nervous system were analyzed. An increased neuronal survival and partial preservation of synaptophysin-positive nerve terminals, related to GDNF and BDNF expression of AT-MSCs, and reduction of pro-inflammatory reaction were observed. In conclusion, AT-MSCs prevent second phase neuronal injury, since they suppressed lymphocyte, astroglia and microglia effects, which finally contributed to rat motor-neuron survival and synaptic stability of the lesioned motor-neuron. Moreover, the survival of the injected AT- MSCs lasted for at least 14 days. These results indicate that neuronal survival after lesion, followed by mesenchymal stem cell (MSC) administration, might occur through cytokine release and immunomodulation, thus suggesting that AT-MSCs are promising cells for the therapy of neuronal lesions.

Highlights

The present study investigates the effects of xenotransplantation of Adipose Tissue Mesenchymal Stem Cells (AT-Mesenchymal stem cells (MSCs)) in animals after ventral root avulsion
Adipose Tissue Mesenchymal Stem Cells (AT-MSCs) were induced into chondrogenic differentiation and differentiated cells produced glycosaminoglycan matrix stained with Alcian blue (Supplement Fig. 2E)
Recent studies suggest stem cell feasibility for treating central nervous system (CNS) diseases and injuries[43,44,45], we proposed the administration of Adipose Tissue Mesenchymal Stem Cells (AT-MSCs) following ventral root avulsion (VRA) in a human/rat xenograft model

Summary

Introduction

The present study investigates the effects of xenotransplantation of Adipose Tissue Mesenchymal Stem Cells (AT-MSCs) in animals after ventral root avulsion. Ventral root avulsion (VRA) at the spinal cord surface induced in Lewis rats, which mimics the brachial plexus injury in humans, was used to investigate the effects of human AT-MSCs xenotransplantation. In this model, injuries to spinal motor neurons in the interface between the central and peripheral nervous system result in a neuronal loss of up to 80% during the first two weeks[19]. The lesion mimics the brachial plexus injury in humans, the most common avulsion injury resulting from motorcycle accidents, leading to motor, sensory or/and autonomic loss of the affected extremity[21]

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