Effects of IGF-1 on neural differentiation of human umbilical cord derived mesenchymal stem cells

Life Sci. 2016 Apr 15:151:93-101. doi: 10.1016/j.lfs.2016.03.001. Epub 2016 Mar 2.

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.

Keywords: Cell proliferation; Insulin-like growth factor-1; Neural differentiation; Umbilical cord derived mesenchymal stem cells.

MeSH terms

  • Adult
  • Astrocytes / drug effects
  • Bone Marrow Cells
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • Insulin-Like Growth Factor I / genetics*
  • Insulin-Like Growth Factor I / pharmacology*
  • Mesenchymal Stem Cells / drug effects*
  • Nestin / biosynthesis
  • Neural Stem Cells / drug effects*
  • PAX6 Transcription Factor / biosynthesis
  • Pregnancy
  • RNA, Small Interfering / pharmacology
  • Umbilical Cord / cytology*
  • Umbilical Cord / drug effects*

Substances

  • Nestin
  • PAX6 Transcription Factor
  • Pax6 protein, rat
  • RNA, Small Interfering
  • Insulin-Like Growth Factor I