Dopaminergic neurons derived from BG01V2 : a variant of human embryonic stem cell line BG01

•  Background and Purpose: Human embryonic stem cells (hESC) areconsidered a renewable source of dopamine producing neurons, and are of particularinterest for their potential clinical use in Parkinson’s disease. In this study, wecharacterized human dopaminergic neurons generated by stromal-derived inducingactivity (SDIA) from BG01V2, a strain of human embryonic stem cell line, BG01,characterized by a chromosome 17 trisomy. Similar chromosomal changes have beenrepeatedly observed in hESC cultures in different laboratories, indicating the importanceof chromosome 17 for growth and adaptation of hESC to culture. Methods: Weinvestigated in vitro proliferation of differentiating cells using a BrDU incorporationassay, and monitored the cell population in long term cultures. Despite the cytogeneticabnormality, TH+ neurons were postmitotic at all stages of differentiation. After 30 daysof differentiation, cell division ceased in 91% of the overall population of cells in theculture, indicating intact cell cycle regulation. Results: Expression of midbrain specificmarker genes (Otx2, Pax5, Msx-1) showed differentiation of hESC-derived neuralprogenitor cells into midbrain specific dopamine neurons. These neurons expressed thedopamine transporter (DAT), and displayed functional DAT activity and electricalexcitability. Conclusions: TH+ cells derived from the BG01V2 hESC line using SDIAare postmitotic and have functional characteristics of normal dopaminergic neurons.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

Nyckelord

SDIA

embryonic stem cells

human

dopaminergic neuron

PA6 cells

Biology

Biologi

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