hTERT-immortalized mesenchymal stem cell-derived EV treatment reduces ZIKV-induced cortical neuronal death, infection, and exosome-mediated transmission

Zika virus (ZIKV), a mosquito-borne flavivirus that vertically transmits from pregnant women to her fetus, causes microcephaly, a birth defect where newborns show smaller head circumference and brain size compared to normal healthy babies. Microcephalic newborns exhibit several developmental delays and neurological complications. There is no cure or potential therapeutics available to treat ZIKV-caused microcephaly. Human telomerase reverse transcriptase (hTERT)-immortalized mesenchymal stem cell (MSC)-derived extracellular vesicles (MSC-EVs) have been recently proposed as potential therapeutics in the treatment of various diseases, including cancer, neurological disorders, and viral infections. We hypothesized an important role of hTERT MSC-EVs in providing neuroprotective effects upon ZIKV infection in murine cortical neurons. Our study opens new thoughts on how hTERT-MSC-EV could be proposed as potential therapeutics in ZIKV-caused microcephaly, where they enhance cell viability, inhibit apoptosis, and reduce viral infection and exosome-mediated transmission/dissemination of ZIKV-infected murine cortical neurons in embryonic brains.