Third trimester amniotic fluid cells improve motor recovery in a mouse model of Spinal Cord Injury

The Spinal Cord Injury (SCI) is a traumatic event characterized by a primary mechanical damage followed by secondary inflammatory processes which amplified the primary lesion. The main treatment following surgery is based on methylprednisolone, although its efficacy has been put into question because of small neurological improvements (1-3). The aim of this work was to assess the therapeutic potential of mesenchymal stem cells derived from third trimester amniotic fluid (AFCs) previously characterized in a contusive mouse model of SCI. One week after contusion (4), 106 AF cells from different cultures were i.v. transplanted and motor recovery was evaluated during 5 weeks following the traumatic lesion (5). Immunohistological analysis was performed 28 days after transplantation while to study mRNA or protein expression, in the spinal cord or in other organs, the animals were sacrificed 2 and 7 days after AFCs graft. Although these cells do not localize exclusively in the lesioned site, but distribute in various organs (lungs, liver, kidneys), the transplantation resulted effective in improving the motor performance. Histochemical analysis revealed a reduced loss of myelin compared to controls, an increased number of microvessels and a lower number of macrophage in the cells treated animals compared to the controls. By means of real-time PCR analysis we observed an increased transcription of genes involved in angiogenic, antiapoptotic and trophic functions. Notably mouse IL1 mRNA level is higher in lung of AFC- vs vehicle-treated mice. In vitro experiments showed that IL1 treated AFCs produce significant high levels of HGF, suggesting that in vivo the cells might respond to the raise of IL1 producing HGF. In conclusion some AFC cultures are able to induce a significant improvement in motor recovery after a SCI in mice by means of a neuroprotective action which seems to involve the activation of the angiogenic pathway. Bracken MB, Shepard MJ, Holford TR, et al. (1998) J Neurosurg89:699–706. Short DJ, El Masry WS, Jones PW. (2000) Spinal Cord 38:273–86. Coleman WP, Benzel E, Cahill DW, et al. (2000) J Spinal Disord 13:185–99 Bottai D, et al. (2010) Exp Neurol 223(2):452-463. Basso DM, et al. (2006) J Neurotrauma 23(5):635-659.