Title:Transplantation of BDNF Gene Recombinant Mesenchymal Stem Cells and Adhesive Peptide-modified Hydrogel Scaffold for Spinal Cord Repair
Volume: 18
Issue: 1
Author(s): Li-Ming Li, Ling-Ling Huang, Xin-Chi Jiang, Jia-Chen Chen, Hong-Wei OuYang and Jian-Qing Gao *
Affiliation:
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang,China
Keywords:
Gene transfection, Mesenchymal stem cells, Spinal cord injury, Brain derived neurotrophic factor, Hydrogel scaffold,
Adhesive peptide.
Abstract: Introduction: Mesenchymal Stem Cells (MSCs) are promising candidates for nerve tissue
engineering. Brain Derived Neurotrophic Factor (BDNF) secreted by MSCs can function to increase
neural differentiation and relieve inflammation response. Gene transfection technology is an efficient
strategy to increase the secretion levels of cytokines and enhance cellular functions. However, transfection
and in vivo gene expression of environmentally sensitive stem cells have been one of the most
challenging subjects due to the requirement in both safety and transfection efficiency. In this study,
gene transfection technology was applied to prepare BDNF gene recombinant MSCs based on our
previously reported liposomal vector ScreenFect® A. To improve cellular survival and gene expression
after in situ implantation of MSCs, an adhesive peptide modified hydrogel scaffold was constructed
using hyaluronic acid. The scaffold was optimized and modified with an adhesive peptide
PPFLMLLKGSTR. The transfected MSCs exhibited improved cellular survival and sustained gene
expression in the three-Dimentional (3D) scaffold in vitro. Compared to untransfected MSCs, gene recombinant
MSCs effectively improved spinal tissue integrity, inhibited glial scar formation and alleviated
inflammatory response. These effects were found discounted when cells were implanted without
the scaffold.
Conclusion: The study developed a promising implantation system for therapy of severe spinal cord
injury and provided the first understanding of Screenfect® A about its functions on stem cell therapy
for nerve tissue repair as well as three-dimentional gene expression.
