Intravenous Bone Marrow Stem Cell Grafts Preferentially Migrate to Spleen and Abrogate Chronic Inflammation in Stroke

Abstract

Background and Purpose—Adult stem cell therapy is an experimental stroke treatment. Here, we assessed homing and anti-inflammatory effects of bone marrow stromal cells (hBMSCs) in chronic stroke.Methods—At 60 days post stroke, adult Sprague–Dawley rats received intravenous hBMSCs (4×106 labeled or nonlabeled cells) or vehicle (saline). A sham surgery group served as additional control. In vivo imaging was conducted between 1 hour and 11 days post transplantation, followed by histological examination.Results—Labeled hBMSCs migrated to spleen which emitted significantly higher fluorescent signal across all time points, especially during the first hour, and were modestly detected in the head region at the 12 hours and 11 days, compared with nonlabeled hBMSCs and vehicle-infused stroke animals, or sham (P<0.05). At 11 days post transplantation, ex vivo imaging confirmed preferential hBMSC migration to the spleen over the brain. Hematoxylin and eosin staining revealed significant 15% and 30% reductions in striatal infarct and peri-infarct area, and a trend of rescue against neuronal loss in the hippocampus. Unbiased stereology showed significant 75% and 60% decrements in major histocompatibility complex II–activated inflammatory cells in gray and white matter, and a 43% diminution in tumor necrosis factor-α cell density in the spleen of transplanted stroke animals compared with vehicle-infused stroke animals (P<0.05). Human antigen immunostaining revealed 0.03% hBMSCs survived in spleen and only 0.0007% in brain. MSC migration to spleen, but not brain, inversely correlated with reduced infarct, peri-infarct, and inflammation.Conclusions—hBMSC transplantation is therapeutic in chronic stroke possibly by abrogating the inflammation-plagued secondary cell death.

Homing and migration of mesenchymal stromal cells: How to improve the efficacy of cell therapy?

“…However, the researchers found that MSC homing to the spleen was important and correlated with a reduced infarct size and peri-infarct inflammation. They propose that MSCs exert a beneficial effect by abrogating secondary, inflammation-related cell death [130] . These data show that tissue-specific MSC homing is important, even though the target tissue is not the brain, as one would expect in a stroke model.…”

Intravenously Delivered Allogeneic Mesenchymal Stem Cells Bidirectionally Regulate Inflammation and Induce Neurotrophic Effects in Distal Middle Cerebral Artery Occlusion Rats Within the First 7 Days After Stroke

“…For example, Acosta et al transplanted MSCs at 30 days after stroke and found a therapeutic effect due to immunosuppression over the next 14 and 30 days [43]. How these MSCs were induced to be immunosuppressive during the chronic phase of stroke remains to be addressed too.…”

Current Stage and Future Perspective of Stem Cell Therapy in Ischemic Stroke

“…Intravenous and intra-arterial route of delivery has the disadvantage that majority of cells are grafted to other organs like lung, liver or spleen and only some cells are founded in the ischemic penumbra [49]. All these potential risk still need to be investigating in order to optimise stem cell therapy in stroke.…”