In Vitro Study of Adipose-Derived Mesenchymal Stem Cells Transduced with Lentiviral Vector Carrying the Brain-Derived Neurotrophic Factor Gene

Int J Stem Cells. 2020 Nov 30;13(3):386-393. doi: 10.15283/ijsc20038.

Abstract

Brain-derived neurotrophic factor (BDNF) exerts its survival-promoting effects on photoreceptors and retinal ganglion cells, however, delivery systems with little-to-no side effect are needed to sustain its controlled release and long-term efficacy. Our previous studies demonstrated that adipose-derived stem cells (ADSCs) are ideal delivery systems for gene therapy; moreover, ADSCs present unique properties like migration to damaged tissue sites, immunomodulation and anti-inflammation. Herein, we propose to employ ADSCs as the BDNF gene delivery vehicle. Different Analyses like flow cytometry, differentiation and cell proliferation assays etc demonstrated that BDNF were successfully transduced into ADSCs and the stemness of ADSCs was maintained even with the transduction. Real Time PCR and Western blot were used to measure mRNA and protein expressions of the BDNF-transduced ADSCs. The results demonstrated that the BDNF expression level of the lentiviral-BDNF transduced ADSCs is significantly increased and, moreover, enhanced the expression of other neurotrophic and downstream signaling factors. The data suggest that ADSCs are a reliable delivery vehicle for BDNF and could be used for the treatment of various diseases.

Keywords: Adipose-derived mesenchymal stem cells; Brain-derived neurotrophic factor; Drug delivery; Lentiviral transduction; Neural protection.