Intravenous Transplantation of Mesenchymal Stem Cells Reduces the Number of Infiltrated Ly6C+ Cells but Enhances the Proportions Positive for BDNF, TNF-1 α, and IL-1 β in the Infarct Cortices of dMCAO Rats

Yunqian Guan; Xiaobo Li; Wenxiu Yu; Zhaohui Liang; Min Huang; Renchao Zhao; Chunsong Zhao; Yao Liu; Haiqiang Zou; Yanli Hao; Zhiguo Chen

doi:10.1155/2018/9207678

Intravenous Transplantation of Mesenchymal Stem Cells Reduces the Number of Infiltrated Ly6C⁺ Cells but Enhances the Proportions Positive for BDNF, TNF-1 α, and IL-1 β in the Infarct Cortices of dMCAO Rats

Stem Cells Int. 2018 Oct 2:2018:9207678. doi: 10.1155/2018/9207678. eCollection 2018.

Authors

Yunqian Guan¹, Xiaobo Li², Wenxiu Yu², Zhaohui Liang², Min Huang², Renchao Zhao², Chunsong Zhao¹, Yao Liu², Haiqiang Zou³, Yanli Hao⁴, Zhiguo Chen¹

Affiliations

¹ Cell Therapy Center, Xuanwu Hospital, Capital Medical University, and Key Laboratory of Neurodegeneration, Ministry of Education, Beijing, China.
² Department of Neurology, Northern Jiangsu People's Hospital, Clinical Medical School of Yangzhou University, Yangzhou, China.
³ Department of Neurology, The General Hospital of Guangzhou Military Command, Guangzhou, China.
⁴ Department of Anatomy, Guangzhou Medical University, Guangzhou, China.

Abstract

The resident microglial and infiltrating cells from peripheral circulation are involved in the pathological processes of ischemia stroke and may be regulated by mesenchymal stem/stromal cell (MSC) transplantation. The present study is aimed at differentiating the neurotrophic and inflammatory roles played by microglial vs. infiltrating circulation-derived cells in the acute phase in rat ischemic brains and explore the influences of intravenously infused allogeneic MSCs. The ischemic brain injury was induced by distal middle cerebral artery occlusion (dMCAO) in SD rats, with or without MSC infusion in the same day following dMCAO. Circulation-derived infiltrating cells in the brain were identified by Ly6C, a majority of which were monocytes/macrophages. Without MSC transplantation, among the infiltrated Ly6C⁺ cells, some were positive for BDNF, IL-1β, or TNF-α. Following MSC infusion, the overall number of Ly6C⁺ infiltrated cells was reduced by 50%. In contrast, the proportions of infiltrated Ly6C⁺ cells coexpressing BDNF, IL-1β, or TNF-α were significantly enhanced. Interestingly, Ly6C⁺ cells in the infarct area could produce either neurotrophic factor BDNF or inflammatory cytokines (IL-1β or TNF-α), but not both. This suggests that the Ly6C⁺ cells may constitute heterogeneous populations which react differentially to the microenvironments in the infarct area. The changes in cellular composition in the infarct area may have contributed to the beneficial effect of MSC transplantation.