Overexpression of TG2 enhances the differentiation of ectomesenchymal stem cells into neuron-like cells and promotes functional recovery in adult rats following spinal cord injury

Ectomesenchymal stem cells (EMSCs) represent a type of adult stem cells derived from the cranial neural crest. These cells are capable of self-renewal and have the potential for multidirectional differentiation. Tissue transglutaminase type 2 (TG2) is a ubiquitously expressed member of the transglutaminase family of Ca(2+)-dependent crosslinking enzymes. However, the effect of TG2 on neural differentiation and proliferation of EMSCs remains unknown. To determine whether TG2 improves EMSC proliferation and neurogenesis, a stable TG2-overexpressing EMSC cell line (TG2-EMSCs) was established by using an adenovirus system. Immunofluorescence staining and western blot analyses demonstrated that TG2 overexpression had beneficial effects on the rate of EMSC neurogenesis, and that the proliferative capacity of TG2-EMSCs was higher than that of controls. Furthermore, the results of western blotting revealed that extracellular matrix (ECM) and neurotrophic factors were upregulated during the differentiation of TG2-EMSCs. Notably, TG2-EMSC transplantation in an animal model of spinal cord injury (SCI), TG2-EMSCs differentiated into neuron-like cells and enhanced the repair of SCI. Taken together, these results demonstrated that TG2 gene transfection may offer a novel strategy to enhance EMSC proliferation and neurogenesis in vivo and in vitro, which may ultimately facilitate EMSC-based transplantation therapy in patients with SCI.