Adipocytes derived from PA6 cells reliably promote the differentiation of dopaminergic neurons from human embryonic stem cells

Abstract

The PA6 stromal cell line comprises a heterogeneous population of cells that can induce both mouse and human embryonic stem cells to differentiate into dopaminergic neurons. This ability of PA6 cells has been termed stromal cell-derived inducing activity (SDIA). The level of SDIA has been found to vary considerably between and within batches of PA6 cells. Not only are the molecular mechanisms that underlie SDIA unknown but also the cell type(s) within the heterogeneous PA6 cultures that underlie SDIA remain poorly defined. In this study, we reveal that adipocytes, which are present within the heterogeneous PA6 cell population, robustly release the factors mediating SDIA. Furthermore, we report that the coculture of human embryonic stem cells with PA6-derived adipocytes reliably induces their differentiation into midbrain dopaminergic neurons.

Safranal-promoted differentiation and survival of dopaminergic neurons in an animal model of Parkinson’s disease

“…Up to 80% of cells expressed the specific cell marker TH, which is the rate-limiting enzyme in the synthesis of DA (Guloglu et al. 2014 ). However, the mechanism of differentiation is unclear, and considering that clinical cell-replacement therapy is a goal of stem cell research, exclusive reaction, and contamination risks may arise from the above method when in contact with animal products.…”

PA6 Stromal Cell Co-Culture Enhances SH-SY5Y and VSC4.1 Neuroblastoma Differentiation to Mature Phenotypes

“…The core components of the PA6 SDIA have been defined as stromal cell-derived factor 1 (SDF-1), pleiotrophin (PTN), insulin-like growth factor (IGF2 and ephrin B1 (EFNB1), collectively termed SPIE factors by Vazin [ 26 ]. In addition to this multiple groups have identified Wnt5a, sonic hedgehog (Shh), secreted frizzled-related protein 1 (sFRP1) and vascular endothelial growth factor D (VEGFD) as contributing factors to SDIA [ 27 ]. Many modified SH-SY5Y differentiation protocols include additional neural-inducing cytokines.…”