Human Mesenchymal Stromal Cells and their Derivative, SB623 Cells, Rescue Neural Cells via Trophic Support following in Vitro Ischemia

Abstract

Cell transplantation is a promising treatment strategy for many neurological disorders, including stroke, which can target multiple therapeutic mechanisms in a sustained fashion. We investigated the ability of human mesenchymal stromal cells (MSCs) and MSC-derived SB623 cells to rescue neural cells via trophic support following an in vitro stroke model. Following oxygen glucose deprivation, cortical neurons or hippocampal slices were cocultured with either MSCs or SB623 cells separated by a semiporous membrane (prohibits cell-cell contact) or with MSC- or SB623 cell-conditioned medium. MSCs, SB623 cells, MSC-conditioned media, and SB623 cell-conditioned media all significantly reduced neural cell damage/death compared to untreated conditions, and the rescue effect of the conditioned media was dose dependent. We identified 11 neurotrophic factors secreted by MSCs and/or SB623 cells. This study emphasizes the importance of trophic support provided by marrow-derived cells, which likely contributes to the efficacy of cell therapy for brain injury.

Effect of Extracellular Vesicles on Neural Functional Recovery and Immunologic Suppression after Rat Cerebral Apoplexy

“…After transplantation of extracellular vesicles, the quantity of B cells, NK cells, and T cells was all increased. Recent studies have confirmed that MSC transplantation can restrain inflammatory reactions involving the brain [21,22]. In the current study, we did not find that changes in cerebral stroke could induce infiltration of immune cells after extracellular vesicle transplantation, which is in contrast to previous reports.…”

Human adipose-derived stem cells for the treatment of intracerebral hemorrhage in rats via femoral intravenous injection

“…One of the possibilities is a mechanism involving the effects of neurotrophic growth factors and/or cytokines generated by the endogenous neural stem cells and the MSC in the huADSC. The infused huADSC may be involved in eliciting repair of tissue damage or regeneration of lost nerve cells to facilitate motional improvement of the ICH induced rats, as speculated by other investigators previously [14,33,34]. Alternatively, the huADSC may participate in angiogenesis or neoangiogenesis, providing better circulation to regenerate lost brain tissue.…”

Opportunities and Challenges: Stem Cell‐Based Therapy for the Treatment of Ischemic Stroke

“…We and other studies demonstrated MSCs treatment increased VEGF expression and angiogenesis in ischemic rats brain [158,159]. In addition, in vitro studies showed that VEGF increased in the conditioned medium of MSCs [160]. Further studies showed that angiogenic gene-modified stem cells had better angiogenic and therapeutic effects for stroke [13,[161][162][163].…”