Abstract
Regardless of enormous translational progress in stem cell clinical application, our knowledge about biological determinants of transplantation-related protection is still limited. In addition to adequate selection of the cell source well dedicated to a specific disease and optimal standardization of all other pre-transplant procedures, we have decided to focus more attention to the impact of culture time and environment itself on molecular properties and regenerative capacity of cell cultured in vitro. The aim of this investigation was to determine neuroprotection-linked cell phenotypic and functional changes that could spontaneously take place when freshly isolated Wharton’s jelly mesenchymal stem cell (WJ-MSC) undergo standard selection, growth, and spontaneous differentiation throughout passaging in vitro. For determining their neuroprotective potential, we used experimental model of human WJ-MSC co-culture with intact or oxygen-glucose-deprived (OGD) rat organotypic hippocampal culture (OHC). It has been shown that putative molecular mechanisms mediating regenerative interactions between WJ-MSC and OHC slices relies mainly on mesenchymal cell paracrine activity. Interestingly, it has been also found that the strongest protective effect is exerted by the co-culture with freshly isolated umbilical cord tissue fragments and by the first cohort of human mesenchymal stem cells (hMSCs) migrating out of these fragments (passage 0). Culturing of WJ-derived hMSC in well-controlled standard conditions under air atmosphere up to fourth passage caused unexpected decline of neuroprotective cell effectiveness toward OGD-OHC in the co-culture model. This further correlated with substantial changes in the WJ-MSC phenotype, profile of their paracrine activities as well as with the recipient tissue reaction evaluated by changes in the rat-specific neuroprotection-linked gene expression.
Highlights
Over the last few years, increasing number of investigations confirmed pro-regenerative, anti-inflammatory, and immunomodulatory potency of cellular therapy that can improve outcomes of brain injuries and block progression of some nowadays incurable neurodegenerative diseases together with reversing of their clinical symptoms
The neuroprotective potential of Wharton’s jelly fragments and Wharton’s jelly-derived mesenchymal stem cell monolayers was estimated in the model of indirect co-culture with organotypic hippocampal slices transiently deprived by oxygen and glucose (OGD) in vitro (Fig. 1)
The neuroprotective effect of the cells at post-ischemic recovery has been measured as the decreasing number of cell death in the vulnerable CA1 region of hippocampal slices (OHC) labeled directly by the propidium iodide (PI)
Summary
Over the last few years, increasing number of investigations confirmed pro-regenerative, anti-inflammatory, and immunomodulatory potency of cellular therapy that can improve outcomes of brain injuries and block progression of some nowadays incurable neurodegenerative diseases together with reversing of their clinical symptoms. One of the most serious problems with the implementation of this therapy to clinic, is that a lot of undertaken trials show inhomogeneous and unstable efficiency partially due to differences in properties and regenerative capacity of the used human mesenchymal stem cell (hMSC) preparations. The patients frequently receive freshly isolated stem cells as a first dose, whether for the injections the cells are propagated by different periods of time in vitro. Despite that this prolonged culture could better fulfill increased needs for cell amounts to therapy, this would change the cell properties important for their regenerative effectiveness
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