Conditioned Medium of Bone Marrow-Derived Mesenchymal Stromal Cells as a Therapeutic Approach to Neuropathic Pain: A Preclinical Evaluation.

Kelly Barbosa Gama,Afrânio Ferreira Evangelista,Ricardo Ribeiro Dos Santos,Adriano Costa De Alcântara,Dourivaldo Silva Santos,Milena Botelho Pereira Soares,Daniela Nascimento Silva,Cristiane Flora Villarreal

doi:10.1155/2018/8179013

Abstract

Neuropathic pain is a type of chronic pain caused by injury or dysfunction of the nervous system, without effective therapeutic approaches. Mesenchymal stromal cells (MSCs), through their paracrine action, have great potential in the treatment of this syndrome. In the present study, the therapeutic potential of MSC-derived conditioned medium (CM) was investigated in a mouse model of neuropathic pain induced by partial sciatic nerve ligation (PSL). PSL mice were treated by endovenous route with bone marrow-derived MSCs (1 × 106), CM, or vehicle. Gabapentin was the reference drug. Twelve hours after administration, neuropathic mice treated with CM exhibited an antinociceptive effect that was maintained throughout the evaluation period. MSCs also induced nonreversed antinociception, while gabapentin induced short-lasting antinociception. The levels of IL-1β, TNF-α, and IL-6 were reduced, while IL-10 was enhanced on sciatic nerve and spinal cord by treatment with CM and MSCs. Preliminary analysis of the CM secretome revealed the presence of growth factors and cytokines likely involved in the antinociception. In conclusion, the CM, similar to injection of live cells, produces a powerful and long-lasting antinociceptive effect on neuropathic pain, which is related with modulatory properties on peripheral and central levels of cytokines involved with the maintenance of this syndrome.

Highlights

Neuropathic pain is a progressive nervous system disease initiated by a primary lesion or dysfunction in the nervous system, commonly caused by a trauma, infection, or ischemia
The therapeutic potential of the conditioned medium (CM) was evaluated in an established partial sciatic nerve ligation (PSL)-induced painful neuropathy model
To determine whether CM induces therapeutic effects in neuropathic states, neuropathic mice were treated with CM, Mesenchymal stromal cells (MSCs), or vehicle seven days after PSL surgery, when the sensorial neuropathy was fully stablished

Summary

Introduction

Neuropathic pain is a progressive nervous system disease initiated by a primary lesion or dysfunction in the nervous system, commonly caused by a trauma, infection, or ischemia. This chronic syndrome is characterized by abnormal sensory symptoms, such as spontaneous pain and an increased response to painful (hyperalgesia) and innocuous (allodynia) stimuli [1,2,3]. The successful control of neuropathic pain is linked to the establishment of new disease-modifying therapeutic approaches. In this context, cell-based therapies represent a promising alternative. Cellular therapies have been considered as a potential successful approach in treating diseases and injuries of the nervous system, for

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