Abstract
Tuning stem cells microenvironment in vitro may influence their regenerative properties. In this study Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) were encapsulated in 3D hydrogels derived from human fibrin (FB) or platelet lysate (PL) and the oxygen level was adjusted to physiological normoxia (5% O2). The influence of the type of the scaffold and physiological normoxia conditions was tested on the WJ-MSCs' survivability, proliferation, migratory potential, the level of expression of selected trophic factors, cytokines, and neural markers. Encapsulated WJ-MSCs revealed high survivability, stable proliferation rate, and ability to migrate out of the hydrogel and the up-regulated expression of all tested factors, as well as the increased expression of neural differentiation markers. Physiological normoxia stimulated proliferation of encapsulated WJ-MSCs and significantly enhanced their neuronal, but not glial, differentiation. Ex vivo studies with indirect co-culture of organotypic hippocampal slices and cell-hydrogel bio-constructs revealed strong neuroprotective effect of WJ-MSCs against neuronal death in the CA1 region of the rat hippocampus. This effect was potentiated further by FB scaffolds under 5% O2 conditions. Our results indicating significant effect of oxygen and 3D cytoarchitecture suggest the urgent need for further optimization of the microenvironmental conditions to improve therapeutical competence of the WJ-MSCs population.
Highlights
Tissue engineering and regenerative medicine are currently vast and rapidly growing research fields
This study indicates that physiological normoxia and 3D microenvironmental conditions induce positive neuroprotective and immunomodulatory response of Wharton’s Jelly-derived mesenchymal stem cells (WJ-Mesenchymal stem/stromal cells (MSCs)) in injured neuronal tissue, which is significantly different as compared to the control, 2D conditions
The Wharton’s Jelly (WJ)-MSCs were seeded in two types of hydrogels: scaffolds made from platelet lysate (PL)
Summary
Tissue engineering and regenerative medicine are currently vast and rapidly growing research fields. In pursuit of the ultimate goal of developing artificial tissues similar to native ones, several preconditioning factors of stem cell culture were performed, including: reduced oxygen level (physiological normoxia) instead of commonly used atmospheric level (21% O2), optimal stem cell density, specific growth media composition, 3D versus 2D culture with different types of 3D scaffold itself. Taking together, they warrant the need for further evaluation[5]. Harvesting these cells does not pose any threat to the donor and incurs minimal costs
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