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

• Published in: Brain research Vol. 1712; pp. 139 - 150
• Main Authors: Tatebayashi, Kotaro, Takagi, Toshinori, Fujita, Mitsugu, Doe, Nobutaka, Nakagomi, Takayuki, Matsuyama, Tomohiro, Yoshimura, Shinichi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2019
• Subjects: Adipose-derived stem cells; Cell transplantation; Cerebral infarction; Macrophage; MCAO; Cerebral infarction; MCP-1; BICs; Adipose-derived stem cells; iPS; ES; MSCs; ADSCs; hADSCs; FBS; AHA; Cell transplantation; Macrophage
• ISSN: 0006-8993; 1872-6240; 1872-6240
• DOI: 10.1016/j.brainres.2019.01.037

•We successfully induced hADSCs using serum-free media.•hADSCs can improve the neurobehavioral deficits after cerebral infarction.•The therapeutic effects are mediated by CD11b+CD163+ macrophages in infarcted lesions. 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. 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). 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.