Overexpression of FOXQ1 enhances anti-senescence and migration effects of human umbilical cord mesenchymal stem cells in vitro and in vivo.

Abstract

Mesenchymal stem cells (MSCs) are unique precursor cells characterized by active self-renewal and differentiation potential. These cells offer the advantages of ease of isolation and limited ethical issues as a resource and represent a promising cell therapy for neurodegenerative diseases. However, replicative senescence during cell culture as well as low efficiency of cell migration and differentiation after transplantation are major obstacles. In our previous study, we found that FOXQ1 binds directly to the SIRT1 promoter to regulate cellular senescence and also promotes cell proliferation and migration in many tumor cell lines. Currently, little is known about the effects of FOXQ1 on normal somatic cells. Therefore, we examine the effects of FOXQ1 on senescence and migration of MSCs. Lentiviral vector-mediated overexpression of FOXQ1 in human umbilical cord mesenchymal stem cells (hUC-MSCs) resulted in enhanced cell proliferation and viability. Furthermore, the expression of proteins and markers positively associated with senescence (p16, p21, p53) was reduced, whereas expression of proteins negatively associated with senescence (SIRT1, PCNA) was promoted. Following transplantation of hUC-MSCs overexpressing FOXQ1 in an animal model of Alzheimer's disease (APPV717I transgenic mice) resulted in amelioration of the effects of Alzheimer's disease (AD) on cognitive function and pathological senescence accompanied the increased numbers of hUC-MSCs in the AD brain. In conclusion, FOXQ1 overexpression promotes anti-senescence and migration of hUC-MSCs in vitro and in vivo. These findings also suggest that this strategy may contribute to optimization of the efficiency of stem cell therapy.