Adipose-derived stem cell therapy inhibits the deterioration of cerebral infarction by altering macrophage kinetics

Introduction: We previously established a method to isolate and culture human adipose-derived stem cells (hADSCs) using fetal bovine serum and showed the therapeutic impact on cerebral infarction. Recently, we modified the culture method with the use of serum-free media for future clinical applications. This study aims to evaluate whether intravenous administration of hADSCs induced by the serum-free culture method would improve neurobehavioral deficits in mice with cerebral infarction. Results: Induced hADSCs possessed the characteristics of mesenchymal stem cells and withstood a freeze-thaw process. hADSC administration improved neurobehavioral deficits in MCAO-treated mice and suppressed brain atrophy at the chronic phase. Although hADSC administration did not affect serum cytokine profiles, it decreased the number of CD11b(+) monocytes in the spleen. Concomitantly, hADSC administration increased the local accumulation of CD11b(+) CD163(+) M2 macrophages into the border zone of the cerebral infarction at 4 days post-MCAO (the acute phase). Discussion: Our data indicate that the systemic administration of hADSCs can improve the neurobehavioral deficits that occur after cerebral infarction by modulating the acute immune response mediated by CD11b(+)CD163(+) M2 macrophages in infarcted lesions.