Human induced pluripotent stem cells differentiation into oligodendrocyte progenitors and transplantation in a rat model of optic chiasm demyelination

• Published in: PloS one 2011-11, Vol.6 (11), p.e27925-e27925
• Main Authors: Pouya, Alireza, Satarian, Leila, Kiani, Sahar, Javan, Mohammad, Baharvand, Hossein
• Format: Article
• Language: English
• Subjects: Animals; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Biology; Biomarkers; Cell Differentiation; Cells, Cultured; Demyelinating Diseases - surgery; Demyelination; Differentiation; Embryonic stem cells; Embryos; Enrichment; Fluorescent Antibody Technique; Gene Expression; Glial stem cells; Humans; Immunofluorescence; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; Male; Mechanical properties; Myelin proteolipid protein; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Olig2 protein; Oligodendrocyte Transcription Factor 2; Oligodendrocytes; Oligodendroglia - cytology; Oligodendroglia - metabolism; Oligodendroglia - transplantation; Optic chiasm; Optic Chiasm - pathology; Optic Chiasm - surgery; Pluripotency; Polymerase chain reaction; Positive selection; Rats; Rats, Sprague-Dawley; Receptor, Platelet-Derived Growth Factor alpha - genetics; Receptor, Platelet-Derived Growth Factor alpha - metabolism; Recovery; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Science; Sox10 protein; SOXE Transcription Factors - genetics; SOXE Transcription Factors - metabolism; Stem cell research; Stem cell transplantation; Stem Cell Transplantation - methods; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Transplantation; Transplantation, Heterologous; Treatment Outcome; Visual evoked potentials
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0027925

This study aims to differentiate human induced pluripotent stem cells (hiPSCs) into oligodendrocyte precursors and assess their recovery potential in a demyelinated optic chiasm model in rats. We generated a cell population of oligodendrocyte progenitors from hiPSCs by using embryoid body formation in a defined medium supplemented with a combination of factors, positive selection and mechanical enrichment. Real-time polymerase chain reaction and immunofluorescence analyses showed that stage-specific markers, Olig2, Sox10, NG2, PDGFRα, O4, A2B5, GalC, and MBP were expressed following the differentiation procedure, and enrichment of the oligodendrocyte lineage. These results are comparable with the expression of stage-specific markers in human embryonic stem cell-derived oligodendrocyte lineage cells. Transplantation of hiPSC-derived oligodendrocyte progenitors into the lysolecithin-induced demyelinated optic chiasm of the rat model resulted in recovery from symptoms, and integration and differentiation into oligodendrocytes were detected by immunohistofluorescence staining against PLP and MBP, and measurements of the visual evoked potentials. These results showed that oligodendrocyte progenitors generated efficiently from hiPSCs can be used in future biomedical studies once safety issues have been overcome.