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Xeno‐free culture for generation of forebrain oligodendrocyte precursor cells from human pluripotent stem cells
Author(s) -
Hermanto Yulius,
Maki Takakuni,
Takagi Yasushi,
Miyamoto Susumu,
Takahashi Jun
Publication year - 2019
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.24413
Subject(s) - forebrain , olig2 , biology , induced pluripotent stem cell , neuroscience , neural stem cell , transplantation , oligodendrocyte , neurosphere , stem cell , microbiology and biotechnology , cellular differentiation , central nervous system , myelin , embryonic stem cell , adult stem cell , medicine , genetics , gene
Oligodendrocytes (OLs) show heterogeneous properties that depend on their location in the central nervous system (CNS). In this regard, the investigation of oligodendrocyte precursor cells (OPCs) derived from human pluripotent stem cells (hPSCs) should be reconsidered, particularly in cases of brain‐predominant disorders for which brain‐derived OPCs are more appropriate than spinal cord‐derived OPCs. Furthermore, animal‐derived components are responsible for culture variability in the derivation and complicate clinical translation. In the present study, we established a xeno‐free system to induce forebrain OPCs from hPSCs. We induced human forebrain neural stem cells (NSCs) on Laminin 511‐E8 and directed the differentiation to the developmental pathway for forebrain OLs with SHH and FGF signaling. OPCs were characterized by the expression of OLIG2, NKX2.2, SOX10, and PDGFRA, and subsequent maturation into O4 + cells. In vitro characterization showed that >85% of the forebrain OPCs (O4 + ) underwent maturation into OLs (MBP + ) 3 weeks after mitogen removal. Upon intracranial transplantation, the OPCs survived, dispersed in the corpus callosum, and matured into (GSTπ + ) OLs in the host brains 3 months after transplantation. These findings suggest our xeno‐free induction of forebrain OPCs from hPSCs could accelerate clinical translation for brain‐specific disorders.