(346f) Differential Effects of Extracellular Vesicles of Lineage-Specific Human Pluripotent Stem Cells on Cellular Behaviours of Isogenic Cortical Spheroids
- Conference: AIChE Annual Meeting
- Year: 2019
- Proceeding: 2019 AIChE Annual Meeting
- Group: Food, Pharmaceutical & Bioengineering Division
- Time: Tuesday, November 12, 2019 - 2:00pm-2:18pm
Method: In this study, the physical and biological properties of EVs isolated from (1) hiPSC-derived neural progenitors (ectoderm), (2) hiPSC-derived cardiac cells (mesoderm), and the undifferentiated hiPSCs, including (3) healthy iPSK3 line and (4) Alzheimerâs disease associated SY-UBH line, were analyzed.
Results: Nanoparticle tracking analysis and electron microscopy results indicate that the derived EVs have the average size of 100-250 nm. Western blot analyses revealed that exosomal markers Alix, CD63, HSC70, and TSG101 were expressed in the derived EVs. MicroRNAs including miR-133, miR-155, miR-221, and miR-34a were differently expressed in different EV groups. Treating the cortical spheroids with different EVs in vitro showed the differential abilities of increasing cell proliferation (indicated by BrdU+ cells) and axonal growth (indicated by Î²-tubulin III staining). For the AÎ²42 oligomer treated cultures, the derived EVs increased cell viability and reduced oxidative stress differentially, showing neural protective ability.
Conclusions: Our results demonstrate that the paracrine signaling provided by tissue context-dependent EVs derived from hiPSCs elicit distinct signaling to impact the physiological state of cortical spheroids. This study should advance our understanding of cell-cell communications in stem cell microenvironment and provide possible therapeutic options for treating neural degeneration.
This study was supported by NSF CAREER (1652992) and NIH R03NS102640.