Font Size: 

Rett syndrome (RTT) is an X-linked dominant severe neurodevelopmental disorder caused by methy-CpG-binding protein 2 (MECP2) gene. MECP2 regulates brain -derived neurotrophic factor (BDNF) and experiments to increase BDNF showed ameliorating symptoms of RTT. However, clinical application of BDNF is difficult because of short half life and low penetrance across the blood-brain barrier. In this study BDNF secreting mesenchymal stem cells (MSC) were generated originating from human umbilical cord (UC) using CRISPR-Cas9. The effect of BDNF-MSC was studied in MECP2 knock down cells and MECP2 deficient mice. AS a result, BDNF-MSC increased pAKT, pERK1/2 and decreased pp38 in vitro and in vivo assay. In vivo study, BDNF-MSC increased body and brain weight. It alsi increased neuronal cell numbers in huppocampus, cortex and striatum. BDNF-MSC increase BDNF and BDNF downstreams such as pAKT, pEKK1/2 for a long period and they have protective effect on RTT. In conclusion, BDNF-MSC generated by CRISPR-Cas9 can be a therapeutic strategy of RTT.

Rett syndrome, MECP2, Brain-Derived Neurotrophic Factor, CRISPR-Cas System, Transplantation, Mesenchymal Stem Cell