Investigations of stem cell therapy for neurological disorders have primarily focused on the grafted cells’ effects within the local brain tissue. Despite mounting evidence of a massive peripheral inflammatory response accompanying stroke, the ability of intracerebrally transplanted cells to migrate to the periphery and sequester systemic inflammation remains unexplored. We previously reported that intravenously transplanted human bone marrow stem cells (hBMSCs) preferentially migrate to spleen, subsequently abrogating chronic inflammation in stroke. Here, we tested the hypothesis that intracerebrally transplanted stem cells in the brain of adult rats subjected to experimental stroke can migrate to the spleen, a vital organ that confers peripheral inflammation after stroke. Immunofluorescence microscopy revealed stem cells engrafted in the brain, but interestingly a specialized band of stem of cells homed to the spleen via lymphatic vessels, seemingly propelled by inflammatory signals. Mechanism-based in vitro studies using hBMSCs co-cultured with lymphatic endothelial cells or microglia, and treated with TNF-alpha further implicated the key role of the lymphatic system in directing stem cell migration and in dampening inflammation. Altogether, the results suggest a robust therapeutic outcome in stroke can be achieved by targeting the systemic inflammatory response. This study is the first to demonstrate brain‑to‑periphery migration of stem cells, advancing the novel concept of harnessing the lymphatic system in mobilizing stem cells to sequester peripheral inflammation as a brain repair strategy. FINANCIAL SUPPORT: CVB is supported by the National Institutes of Health.
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.