Exploring mesenchymal stem cells as delivery vehicles for neuropathic pain treatment

Abstract

ABSTRACT : Neuropathic pain (NP) is a debilitating chronic syndrome that is often refractory to currently available analgesics. Previous studies conducted by our group provided insight into the relevant role of the overexpression of the miR-30c-5p in the development of NP in rats after peripheral nerve injury and the anti-allodynic effect achieved by administration of miR-30c-5p inhibitor. One of the most concerning drawbacks of using micro RNAs-based therapies is their poor targeting abilities and off target effects. To overcome these barriers, tissue specific controlled delivery strategies must be addressed. In this regard, some preclinical studies in NP models sustain that intrathecal injected mesenchymal stem cells (MSCs) specifically migrate to damaged tissues of the central nervous system and present a significant anti-allodynic effect. In this work, we propose the immortalized line of MSCs derived from adipose tissue, ASC52telo, as a delivery vehicle of miR-30c-5p inhibitor in a NP model. We demonstrated that ASC52telo intrathecally administered successfully reached the damaged dorsal root ganglia and attenuated the development of mechanical allodynia in neuropathic rats. To assess the capability of ASC52telo to transport the miR-30c-5p inhibitor, we evaluated the transfection efficiency of two chemical reagents (Lipofectamine RNAiMAX and X-TremeGENE) to transfer a fluorescently labelled miR-30c-5p inhibitor into these cells. Our results show that X-TremeGENE presented a transfection success of 70% accompanied by a cell viability higher than 80%. These preliminary results show ASC52telo as a promising novel strategy to deliver miR-30c-5p inhibitor to target tissues and thus, potentiate its anti-allodynic effect in a rat model of NP.