Human stem cells transplanted into the rat stroke brain migrate to the spleen via lymphatic and inflammation pathways
Autor: | Julian P. Tuazon, Kaya Xu, Cesario V. Borlongan, Harry R. van Loveren, Yuji Kaneko, Fernando L. Vale, Jea Young Lee |
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Rok vydání: | 2018 |
Předmět: |
Male
Pathology medicine.medical_specialty government.form_of_government Spleen Inflammation Mesenchymal Stem Cell Transplantation Systemic inflammation Article Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Therapy & Immunotherapy Animals Humans Medicine Lymphatic Vessels 030304 developmental biology Brain Diseases 0303 health sciences Microglia business.industry Graft Survival Mesenchymal stem cell Mesenchymal Stem Cells Hematology Rats Stroke Lymphatic Endothelium medicine.anatomical_structure Lymphatic system government medicine.symptom Stem cell business 030217 neurology & neurosurgery |
Zdroj: | Haematologica |
ISSN: | 1592-8721 0390-6078 |
Popis: | 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 unexamined. Here, we tested the hypothesis that human bone marrow mesenchymal stromal cells intracerebrally transplanted in the brain of adult rats subjected to experimental stroke can migrate to the spleen, a vital organ that confers peripheral inflammation after stroke. Sham or experimental stroke was induced in adult Sprague-Dawley rats by a 1 hour middle cerebral artery occlusion model. One hour after surgery, rats were intracerebrally injected with human bone marrow mesenchymal stromal cells (3×105/9 μL), then euthanized on day 1, 3, or 7 for immunohistochemical assays. Cell migration assays were performed for human bone marrow mesenchymal stromal cells using Boyden chambers with the bottom plate consisting of microglia, lymphatic endothelial cells, or both, and treated with different doses of tumor necrosis factor-α. Plates were processed in a fluorescence reader at different time points. Immunofluorescence microscopy on different days after the stroke revealed that stem cells engrafted in the stroke brain but, interestingly, homed to the spleen via lymphatic vessels, and were propelled by inflammatory signals. Experiments using human bone marrow mesenchymal stromal cells co-cultured with lymphatic endothelial cells or microglia, and treated with tumor necrosis factor-α, further indicated the key roles of the lymphatic system and inflammation in directing stem cell migration. 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. |
Databáze: | OpenAIRE |
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