Lei Zhao1, Yetong Feng2, Xin Chen3, Jing Yuan1, Xiaobo Liu4, Yaoyu Chen4, Yifan Zhao4, Pengfei Liu5, Yalan Li6. 1. Department of Anesthesiology, Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, PR China. 2. Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, PR China. Electronic address: fengyt11@sina.com. 3. Department of Laboratory Medicine, Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, PR China. 4. Department of Regenerative Medicine, School of Pharmaceutical Science, Jilin University, Changchun, PR China; Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, PR China. 5. Department of Regenerative Medicine, School of Pharmaceutical Science, Jilin University, Changchun, PR China; Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, PR China. Electronic address: rockman123456@sina.com. 6. Department of Anesthesiology, First Affiliated Hospital of Jinan University, Guangzhou, PR China. Electronic address: tyalan@jnu.edu.cn.
Abstract
AIMS: Umbilical cord derived mesenchymal stem cells (UC-MSCs) have been demonstrated to hold the potential to be applied in the treatment of kinds of disease. In recent years, some scientists have differentiated the cells into neural progenitor cells (NPCs) successfully, providing a new cell source for neural disease therapy. However, the differentiation methods still need to be improved for the clinical studies in the future. In this study, insulin-like growth factor-1 (IGF-1) was tested to ameliorate UC-MSCs neural differentiation. MAIN METHODS: IGF-1 overexpressing UC-MSCs (UC-MSCs-IGF-1) were established through retroviral infection, and further differentiated into NPCs through neural induction. The proliferation and differentiation ability of UC-MSCs derived NPCs were evaluated respectively and the associated signaling mechanisms were further analyzed with RNA microarray, qPCR and western-blot. KEY FINDINGS: Compared with NPCs from normal UC-MSCs, the NPCs derived from UC-MSCs-IGF-1 hold better proliferation ability and more Pax6-positive cells and Nestin-positive cells. Moreover, the UC-MSCs-IGF-1 derived NPCs could differentiate into astrocyte with higher efficiency during the process of terminal differentiation in vitro. RNA microarray analysis indicated that some key genes associated with neural differentiation and NPCs proliferation were upregulated, which were also confirmed with qPCR and western-blot. Finally, NPCs from UC-MSCs-IGF-1 transfected with IGF-1-siRNA showed a decrease of proliferation ability and astrocyte differentiation. SIGNIFICANCE: This study indicated that IGF-1 could improve neural differentiation of human UC-MSCs and provided a novel strategy to enhance astrocyte differentiation of NPCs from UC-MSCs.
AIMS: Umbilical cord derived mesenchymal stem cells (UC-MSCs) have been demonstrated to hold the potential to be applied in the treatment of kinds of disease. In recent years, some scientists have differentiated the cells into neural progenitor cells (NPCs) successfully, providing a new cell source for neural disease therapy. However, the differentiation methods still need to be improved for the clinical studies in the future. In this study, insulin-like growth factor-1 (IGF-1) was tested to ameliorate UC-MSCs neural differentiation. MAIN METHODS:IGF-1 overexpressing UC-MSCs (UC-MSCs-IGF-1) were established through retroviral infection, and further differentiated into NPCs through neural induction. The proliferation and differentiation ability of UC-MSCs derived NPCs were evaluated respectively and the associated signaling mechanisms were further analyzed with RNA microarray, qPCR and western-blot. KEY FINDINGS: Compared with NPCs from normal UC-MSCs, the NPCs derived from UC-MSCs-IGF-1 hold better proliferation ability and more Pax6-positive cells and Nestin-positive cells. Moreover, the UC-MSCs-IGF-1 derived NPCs could differentiate into astrocyte with higher efficiency during the process of terminal differentiation in vitro. RNA microarray analysis indicated that some key genes associated with neural differentiation and NPCs proliferation were upregulated, which were also confirmed with qPCR and western-blot. Finally, NPCs from UC-MSCs-IGF-1 transfected with IGF-1-siRNA showed a decrease of proliferation ability and astrocyte differentiation. SIGNIFICANCE: This study indicated that IGF-1 could improve neural differentiation of human UC-MSCs and provided a novel strategy to enhance astrocyte differentiation of NPCs from UC-MSCs.
Authors: Gang Chen; Xiongqi Zhao; Zedan Tan; Dongdong Wang; Ding Luo; Peiyao Zhang; Jun Cao; Fan Wang; Qiyu Liu; Li Li Journal: Mol Med Rep Date: 2018-06-29 Impact factor: 2.952