Original Research ARTICLE

Front. Integr. Neurosci., 01 December 2011 | http://dx.doi.org/10.3389/fnint.2011.00079

Long-lasting effects of human mesenchymal stem cell systemic administration on pain-like behaviors, cellular, and biomolecular modifications in neuropathic mice

Dario Siniscalco1*, Catia Giordano1, Umberto Galderisi2, Livio Luongo1, Vito de Novellis1, Francesco Rossi1 and Sabatino Maione1*
  • 1 Division of Pharmacology “L. Donatelli,” Department of Experimental Medicine, Second University of Naples, Naples, Italy
  • 2 Division of Biotechnology and Molecular Biology “A. Cascino,” Second University of Naples, Naples, Italy

Background: Neuropathic pain (NP) is an incurable disease caused by a primary lesion in the nervous system. NP is a progressive nervous system disease that results from poorly defined neurophysiological and neurochemical changes. Its treatment is very difficult. Current available therapeutic drugs have a generalized nature, sometime acting only on the temporal pain properties rather than targeting the several mechanisms underlying the generation and propagation of pain. Methods: Using biomolecular and immunohistochemical methods, we investigated the effect of the systemic injection of human mesenchymal stem cells (hMSCs) on NP relief. We used the spared nerve injury (SNI) model of NP in the mouse. hMSCs were injected into the tail vein of the mouse. Stem cell 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. Results: hMSCs were able to reduce pain-like behaviors, such as mechanical allodynia and thermal hyperalgesia, once injected into the tail vein. An anti-nociceptive effect was detectable from day 11 post surgery (7 days post cell injection). hMSCs were mainly able to home in the spinal cord and pre-frontal cortex of neuropathic mice. Injected hMSCs reduced the protein levels of the mouse pro-inflammatory interleukin IL-1β and IL-17 and increased protein levels of the mouse anti-inflammatory interleukin IL-10, and the marker of alternatively activated macrophages CD106 in the spinal cord of SNI mice. Conclusion: As a potential mechanism of action of hMSCs in reducing pain, we suggest that they could exert their beneficial action through a restorative mechanism involving: (i) a cell-to-cell contact activation mechanism, through which spinal cord homed hMSCs are responsible for switching pro-inflammatory macrophages to anti-inflammatory macrophages; (ii) secretion of a broad spectrum of molecules to communicate with other cell types. This study could provide novel findings in MSC pre-clinical biology and their therapeutic potential in regenerative medicine.

Keywords: neuropathic pain, cell transplantation, human mesenchymal stem cells, macrophages

Citation: Siniscalco D, Giordano C, Galderisi U, Luongo L, de Novellis V, Rossi F and Maione S (2011) Long-lasting effects of human mesenchymal stem cell systemic administration on pain-like behaviors, cellular, and biomolecular modifications in neuropathic mice. Front. Integr. Neurosci. 5:79. doi: 10.3389/fnint.2011.00079

Received: 12 September 2011; Accepted: 16 November 2011;
Published online: 01 December 2011.

Edited by:

Hongyun Huang, Neuroscience Institute of Taishan Medical University, China

Reviewed by:

Russell J. Andrews, NASA Ames Research Center, USA
Lin Chen, Beijing Hongtianji Neuroscience Academy, China

Copyright: © 2011 Siniscalco, Giordano, Galderisi, Luongo, de Novellis, Rossi and Maione. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.

*Correspondence: Dario Siniscalco and Sabatino Maione, Division of Pharmacology, Department of Experimental Medicine, Second University of Naples, via S. Maria di Costantinopoli, 16, 80138 Napoli, Italy. e-mail: dariosin@uab.edu; sabatino.maione@unina2.it