Human adipose-derived mesenchymal stromal cells increase endogenous neurogenesis in the rat subventricular zone acutely after 6-hydroxydopamine lesioning

Abstract

Background aims. In Parkinson's disease (PD), neurogenesis in the subventricular zone (SVZ) olfactory bulb (OB) axis is affected as the result of the lack of dopaminergic innervations reaching the SVZ. This aberrant network has been related to the hyposmia of PD patients, which is an early diagnostic marker of the disease. Consequently, much interest arose in finding mechanisms to modulate the SVZ-OB axis. Direct modulation of this axis could be achieved by transplantation of mesenchymal stromal cells (MSC), as it has been shown in rat and mouse PD models. However, the neurogenic effect of MSC in PD was thus far only analyzed weeks after transplantation, and little is known about effects immediately after transplantation. Methods. We assessed the acute neuroprotective and neurogenic effects of adipose-derived MSC transplanted into the rat substantia nigra in the 6-hydroxydopamine model of PD. Results. Three days after transplantation, subventricular neurogenesis was significantly increased in MSC-transplanted versus non-transplanted animals. Most MSC were found in the region of the substantia nigra and the surrounding arachnoid mater, expressing S100 beta and brain-derived neurotrophic factor, whereas some MSC showed an endothelial phenotype and localized around blood vessels. Conclusions. The acute neurogenic effects and neurotrophic factor expression of MSC could help to restore the SVZ-OB axis in PD.