Abstract
Study Design: An experimental in-vitroand in-vivo parallel group study.
Objectives: To investigate the prolonged effects of Zfp521 on gene expression in the U87MG glioma cell line and assess its in vivo impact on animal movement post-transplantation into spinal cord injury (SCI).
Setting: Royan Institute for Stem Cell Biology and Technology Laboratory.
Methods: U87MG cells were transduced with Zfp521-IRES-GFP and maintained in neural inductive medium for over 3 weeks. Gene expression of Gfap, Itga6, Pax6, nestin, Sox1, Tubb3, and Olig2 was analyzed. Transplanted cells' impact on locomotor capacity in SCI was assessed using the Basso-Beattie-Bresnahan (BBB) scale and footprint analysis.
Results: Zfp521 overexpression induced morphological changes and aggregated formation in U87MG cells, with a transfection rate of 26%. Significant upregulation of Pax6, Tubb3, and Olig2 and decreasing of Sox1 were observed, while Gfap, Itga6, and nestin showed non-significant changes. In SCI animals, U87-Zfp521 exhibited substantial recovery in hindlimb motor coordination (BBB score of 12) and weight support. Moreover, gait analysis revealed increased step length, stride angle, and step width in U87-Zfp521 animalsduring a five-week treatment. While plantar application showed no significant improvement.
Conclusions: Controlling Zfp521 expression level prominently enables the neuronal and oligodendrocyte lineage alley in the glioblastoma cell line that can be the potential therapy for promoting recovery in GBM and SCIs, highlighting its role as a promising target for further exploration in neural regeneration strategies.
Sponsorship: This work was funded by Tehran University of Medical Sciences with grant number 97-02-38-39408.