Title : Cell culture preconditioning before transplantation influences the inflammatory response of distant brain regions
Abstract:
Stroke is a significant cause of mortality and disability globally. It can disrupt the blood- brain barrier (BBB), leading to neuroinflammation. Stem cell therapy is a fundamental part of regenerative medicine, enabling the repair or replacement of damaged tissues using living cells. Furthermore, the paracrine properties and immunomodulatory capabilities of mesenchymal stem cells play a crucial role in this therapeutic process.
This study aimed to evaluate the effects of the transplantation of human Wharton's jelly mesenchymal stem cells (WJ-MSCs) into the rat striatum on the hippocampus, a region distant from the transplant site, during the first 7 days after ischemic stroke. Cells were cultured under 21% (standard) or 5% (physiological) oxygen conditions and delivered within either a platelet lysate scaffold or in saline. In adult rats, ischemic stroke was induced following ouabain injection into the striatum. We evaluated the modulation of inflammatory and anti- inflammatory responses, as well as the integrity of the BBB in the rat hippocampus after the injury and following transplantation of human WJ-MSCs into the rat striatum. Quantitative real- time PCR (RT-PCR) and Western blot analyses were performed on the rat hippocampus.
WJ-MSCs cultured under 21% oxygen enhanced blood-brain barrier repair by upregulating tight junction proteins, but also promoted neuroinflammation. In contrast, WJ- MSCs preconditioned in physioxia stabilized BDNF signaling, reduced Galectin–3–linked neuroinflammation, and activated the ERK1/2-c-Fos pathway. Encapsulation in a scaffold helped the cells to mitigate the pro-inflammatory effects.
WJ-MSC culture preconditioning before transplantation plays a crucial role in shaping their therapeutic effects at sites distant from the graft location. Therefore, to use stem cells in translational medicine, it is essential to establish appropriate in vitro conditions for cell preconditioning, ensuring that the cells acquire the necessary properties to treat specific disorders and achieve the desired therapeutic effect.
