Over the last decade a large number of studies explored the use of cord-blood-derived stem cells for treatment of neurological disorders. Despite of some positive preclinical results low survival of transplanted cells was noticed in the host brain. It seems that transplantation of the donor cells in their own milieu might be more effective due to the natural cell-cell contact and the presence of growth factors and cytokines. The concept of our studies was to deliver human stem cells resided in Wharton jelly (WJ) of umbilical cord tissue into rat brain. 3D tissue implant contains mesenchymal stem cells (MSCs) capable of multilineage differentiation. In the current study we performed in situ analysis of entire WJ-MSCs after their transplantation into: hippocampal organotypic slices isolated from neonatal rats (i); the striatum of normal (ii) or focally injured (iii) adult Wistar rats. Results: Seven days after grafting on hippocampal slices intense migration of the donor cells (NuMa+) from 3D WJ implant was noticed. Double-labeling showed co-localization of NuMa marker with NF200 or GFAP activity in these cells whereas donor cells residing in 3D WJ implant did not express any neural markers. Interestingly, in intact brain all WJ-MSCs (NuMa+) cells remained in 3D tissue implant but differentiated into NF200+ and GFAP+ phenotypes during the time of observation. In contrast, after WJ implantation into injured rat brain the donor MSCs proclaimed migration towards ischemic boundary regions. Moreover, NF200 or GFAP markers were localized among both, migrating as well as remaining in the graft NuMa+ cells. Conclusions: Transplantation of WJ-MSCs in 3D tissue implant into adult rat brain improves cells survival within graft and induces their spontaneous transition into cell of neural lineage. Brain injury additionally stimulates migration of these donor cells out of WJ implant with their further differentiation in the host tissue. Supported by Fondation Jerome Lejeune grant
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