The role of application of mesenchymal stem cells stimulated via alpha-adrenergic receptor in peripheral neuropathy

It has been determined that the stimulation of mesenchymal stem cells (MSCs) via adrenergic receptors affects the migration and proliferation of cells. However, there is no study examining how MSCs stimulated via α-adrenergic receptors affect nerve tissue regeneration in peripheral neuropathy and neuronal markers in cell culture. In our study, we aimed to investigate the effects of MSCs stimulated by α-adrenergic receptor subtypes on motor function, neuropathic pain and histopathologically in nerve-muscle tissue in a peripheral neuropathy model. It was also aimed to determine the levels of growth factors in cell culture, which are thought to play a role in the formation of these effects. The peripheral neuropathy was induced in mice by partial sciatic nerve ligation in our study. MSCs incubated with adrenaline (adrenergic receptor agonist), atipamezole (α2-adrenergic receptor antagonist), prazosin (α1-adrenergic receptor antagonist), phentolamine (α-adrenergic receptor antagonist) and unstimulated MSCs were intramuscularly applied to the lesioned area. The rotarod test was performed at the fourth, sixth, eighth and tenth weeks after the administration of MSC and stimulated MSC groups, and a time-dependent increase in motor functions was detected compared to the neuropathy group. In the cold plate latency test, it was determined that the cold allodynia threshold increased depending on time in the MSC and stimulated MSC groups compared to the neuropathy group, but this increase was less in the α2-adrenergic receptor antagonist applied group. In the 10th week histopathological examination of the sciatic nerve and soleus muscle isolated from the experimental animals showed significant improvement in the MSC and stimulated MSC groups compared to the neuropathy group. In addition, it was determined that the improvement was less in the group which was administered α2-adrenergic receptor antagonist. However, it was determined that NGF, GDNF and VEGF mRNA expressions, which we measured in vitro, were higher in the MSC group with α2-adrenergic receptor blockade compared to the other groups. This study suggests that α2-adrenergic receptors play an important role in the antiallodynic effect of MSCs stimulated by α-adrenergic receptors in the treatment of neuropathic pain and in prolonging the duration of motor functions. Functional and histopathological findings showed that structural and cellular recovery was lower in the group in which MSCs incubated with α2-adrenergic receptor antagonist were administered. These results show that α2-adrenergic receptors have a greater role in the regenerative effect of MSCs.