Title

 

Authors

D. Siniscalco, C. Giordano, L. Luongo, F. Rossi, S. Maione, V. de Novellis

Department of Experimental Medicine, Division of Pharmacoloy; Second University of Naples.
Email: dariosin@uab.edu

 

Abstract

Neuropathic pain is an incurable diseasearised by a primary lesion in the nervous system. We investigated, trough biomolecular and immunohistochemical methods, the effect of human mesenchymal stem cells (hMSCs) systemic injection on neuropathic pain relief. We used spared nerve injury (SNI) model of neuropathic pain in mouse. Human MSCs were injected in the mousetail vein. Stem cells injection was performed 4 days after sciatic nerve surgery. Neuropathic mice were monitored every 10 days starting from day 11 until 90 days after surgery. Human MSCs were able to reduce pain like behaviours, such as mechanical allodynia and thermal hyperalgesia, once injected in the tail vein. Anti-nociceptive effect was detectable from day 11 after surgery (7 days post cell injection). Human MSCs were mainly able to home in spinal cord and pre-frontal cortex of neuropathic mice. Injected hMSCs reduced the protein levels of the mouse pro-inflammatory interleukin IL-1ß and IL-17, and increased the protein levels of the mouse anti-inflammatory interleukin IL-10, as well as the marker of alternatively activated macrophages CD106 in spinal cord of SNI mice. As possible mechanism of action of hMSCs in reducing pain, we suggest that hMSCs could exert their beneficial action through a restorative mechanism involving: i) cell-to-cell contact activation mechanism, through which spinal cord homed hMSCs are responsible to switch pro-inflammatory macrophages to anti-inflammatory macrophages; ii) secretion of a broad spectrum of molecules to communicate to other cell types. This study will give novel findings in MSC pre-clinical biology and in their therapeutic potential in regenerative medicine.

Siniscalco et al. (2010). Cell Mol Life Sci. 67:655-669.
Siniscalco (2010). Methods Mol Biol. 617:337-345.