Human Pluripotent Stem Cells on Cellular Behaviors of Isogenic Cortical Spheroids

Extracellular vesicles (EVs) or exosomes are responsible for a variety of signaling processes and overall physiological and pathological states of stem cells and tissues. Human induced pluripotent stem cells (hiPSCs) have unique characteristics that can mimic embryonic tissue development. EVs derived from hiPSCs can be used as therapeutics, biomarkers, and drug delivery vehicles. One issue is that little is known about the characteristics of secreted EVs/exosomes by hiPSCs during tissue morphogenesis due to paracrine signaling. In this study, EVs derived from hiPSC-derived neural progenitors (ectoderm), hiPSC-derived cardiac cells (mesoderm), and the undifferentiated hiPSCs (healthy iPSK3 and Alzheimer's associated SY-UBH lines) were analyzed. Nanoparticle tracking analysis and electron microscopy results showed that the derived EVs had the average size of 100-250 nm. Western blot revealed that exosomal markers ALIX, CD63, and TSG 101 were expressed in the derived EVs. miRNAs including miR-133 and miR-155 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 assay) and axonal growth (indicated by β-tubulin III staining). For the Aβ42 oligomer treated cultures, the derived EVs increased cell viability and reduced oxidative stress differentially, showing neural protective ability. This study should advance our understanding of cell-cell communications in stem cell microenvironment and provide possible therapeutic options for treating neural degeneration.