The potential application of canine and human mesenchymal stem cells for the treatment of spinal cord injury: an in vitro examination of their neurotrophic and angiogenic activities

Abstract

Traumatic spinal cord injury (SCI) is a devastating event. It causes severe damage to the nervous tissue which can be associated with partial or complete loss of movement and sensation. Recent studies suggested that the benefits of stem cell transplants for SCI may not be restricted to cell restoration alone, e.g. to replace damaged neurons, but also may be due to their capacity to stimulate endogenous cells at wound sites through paracrine activity.Mesenchymal stem/stromal cells (MSCs), in particular, are thought to have anti-inflammatory, neuroprotective, neurotrophic and angiogenic effects and may thus reduce secondary damage and promote neuroregeneration and wound healing after their administration. Experimental studies of small rodent SCI models are currently being used to investigate the MSCs as a promising option for treatments that repair damaged neuronal tissue. However, translation to human patients is still a challenging step. Dogs represent a good large animal model as the causes of SCI in dogs occur naturally and traumatically, and because of the similar scale and heterogeneity of the lesions formed. Therefore, this study aimed to investigate and compare the effects of canine and human MSCs, focused on the effects of MSC conditioned medium (MSC CM) on neurogenesis and angiogenesis using established responder cell lines, i.e. SH-SY5Y neuronal cells and EA.hy926 endothelial cells. All of the MSCs were derived from adipose tissue, and CD271 was used to isolate subset populations from human MSCs. The study has demonstrated for the first time the potentially beneficial effects of canine MSC CM in promoting SH-SY5Y neurite outgrowth and cell proliferation, as well as EA.hy926 endothelial cell proliferation, cell migration and the formation of endothelial tubules. Further experimentation demonstrated that canine and human adipose-derived MSCs exhibited such neurotrophic and angiogenic effects to a similar extent. This may have important implications for the pre-clinical assessment of MSC paracrine activity in the development of cell transplantation protocols both for dogs and humans. Finally, the study compared the neurotrophic and angiogenic effects of MSC CM from selected subpopulations of human MSCs, i.e. CD271+ versus CD271- and plastic adherent MSCs; this was with a view to establishing whether a more homogeneous MSC population might differ in their paracrine activity. There was no significant difference in the neurogenic effects of these various secretomes; however, MSC CM from humanCD271+MSCs was found to be significantly less pro-angiogenic than human CD271- MSCsor non-selected human MSCs. In conclusion, the study supports the use of MSCs to treat naturally occurring SCI in dogs, and suggests that there is no evidence herein to support preselecting   CD271+ cells.