Hypoxic Umbilical Cord-Derived Mesenchymal Stem Cells Decrease TNF-α and IL-1β Levels in an Acute Ischemic Stroke Rat Model

Abstract

Background: Tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) contribute to secondary neuronal injury after ischemic stroke by promoting blood brain barrier disruption and neuronal apoptosis. Mesenchymal stem cells (MSCs) have anti-inflammatory and neuroprotective effects, but their efficacy may be limited under ischemic conditions due to poor survival and inadequate paracrine activity. Hypoxic preconditioning may enhance MSC potency, yet in vivo evidence on cytokine modulation remains limited. This study evaluated the effects of hypoxic-preconditioned umbilical cord MSCs (UC-MSCs) on TNF-α and IL-1β levels in an acute ischemic stroke model.

Materials and methods: Twenty-eight male Wistar rats were randomized into four groups: a healthy control group, an untreated stroke group, and two treatment groups receiving UC-MSCs at doses of 1.5 × 10⁶ and 3.0 × 10⁶ cells, respectively. Stroke was induced using middle cerebral artery occlusion (MCAO). UC-MSCs were administered intravenously on day 3 post-occlusion. Brain tissue TNF-α and IL-1β were measured by ELISA and analyzed using one-way ANOVA with post hoc testing.

Results: Compared with the untreated stroke group, both treatment groups receiving UC-MSCs (1.5×10⁶ and 3.0×10⁶ cells) showed significantly lower TNF-α and IL-1β levels (p<0.001). The reduction was greater in the 3.0 × 10⁶-cell group, indicating a dose-dependent anti-inflammatory effect, with the lowest cytokine levels observed in this group.

Conclusion: Hypoxic UC-MSCs decrease the levels of TNF-α and IL-1β in acute ischemic stroke, supporting their immunomodulatory and neuroprotective potential. Further studies should assess long-term outcomes and histopathological correlations.

Keywords: ischemic stroke, UC-MSCs, hypoxic preconditioning, TNF-α, IL-1β