Peripheral Circulation and Astrocytes Contribute to the MSC-Mediated Increase in IGF-1 Levels in the Infarct Cortex in a dMCAO Rat Model

Xiaobo Li; Wenxiu Yu; Yunqian Guan; Haiqiang Zou; Zhaohui Liang; Min Huang; Renchao Zhao; Chunsong Zhao; Zhenhua Ren; Zhiguo Chen

doi:10.1155/2020/8853444

Peripheral Circulation and Astrocytes Contribute to the MSC-Mediated Increase in IGF-1 Levels in the Infarct Cortex in a dMCAO Rat Model

Stem Cells Int. 2020 Sep 1:2020:8853444. doi: 10.1155/2020/8853444. eCollection 2020.

Authors

Xiaobo Li¹, Wenxiu Yu¹, Yunqian Guan^{2

3}, Haiqiang Zou⁴, Zhaohui Liang¹, Min Huang¹, Renchao Zhao¹, Chunsong Zhao^{2

3}, Zhenhua Ren^{2

3}, Zhiguo Chen^{2

3}

Affiliations

¹ Department of Neurology, Northern Jiangsu People's Hospital, Clinical Medical School of Yangzhou University, Yangzhou, China.
² Cell Therapy Center, Beijing Institute of Geriatrics, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases, Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing 100053, China.
³ Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing 100069, China.
⁴ Department of Neurology, The General Hospital of Guangzhou Military Command, Guangzhou, China.

Abstract

Materials and methods: Ischemic brain injury was induced by dMCAO in Sprague-Dawley rats. The transplantation group received MSC infusion 1 h after dMCAO. Expression of IGF-1 in GFAP+ astrocytes, Iba-1+ microglia/macrophages, CD3+ lymphocytes, Ly6C+ monocytes/macrophages, and neutrophil elastase (NE)+ neutrophils was examined to determine the contribution of these cells to the increase of IGF-1. ELISA was performed to examine IGF-1 levels in blood plasma at days 2, 4, and 7 after ischemia onset.

Results: In total, only 5-6% of Iba-1+ microglia were colabeled with IGF-1 in the infarct cortex, corpus callosum, and striatum at day 2 post-dMCAO. MSC transplantation did not lead to a higher proportion of Iba-1+ cells that coexpressed IGF-1. In the infarct cortex, all Iba-1+/IGF-1+ double-positive cells were also positive for CD68. In the infarct, corpus callosum, and striatum, the majority (50-80%) of GFAP+ cells were colabeled with ramified IGF-1 signals. The number of GFAP+/IGF-1+ cells was further increased following MSC treatment. In the infarct cortex, approximately 15% of IGF-1+ cells were double-positive for CD3. MSC treatment reduced the number of infiltrated CD3+/IGF-1+ cells by 70%. In the infarct, few Ly6C+ monocytes/macrophages or NE+ neutrophils expressed IGF-1, and MSC treatment did not induce a higher percentage of these cells that coexpressed IGF-1. The IGF-1 level in peripheral blood plasma was significantly higher in the MSC group than in the ischemia control group.

Conclusion: The MSC-mediated increase in IGF-1 levels in the infarct cortex mainly derives from two sources, astrocytes in brain and blood plasma in periphery. Manipulating the IGF-1 level in the peripheral circulation may lead to a higher level of IGF-1 in brain, which could be conducive to recovery at the early stage of dMCAO.