1. Academic Validation
  2. Engineered basic fibroblast growth factor-overexpressing human umbilical cord-derived mesenchymal stem cells improve the proliferation and neuronal differentiation of endogenous neural stem cells and functional recovery of spinal cord injury by activating the PI3K-Akt-GSK-3β signaling pathway

Engineered basic fibroblast growth factor-overexpressing human umbilical cord-derived mesenchymal stem cells improve the proliferation and neuronal differentiation of endogenous neural stem cells and functional recovery of spinal cord injury by activating the PI3K-Akt-GSK-3β signaling pathway

  • Stem Cell Res Ther. 2021 Aug 21;12(1):468. doi: 10.1186/s13287-021-02537-w.
Feifei Huang  # 1 Tianyun Gao  # 1 Wenqing Wang 1 Liudi Wang 1 Yuanyuan Xie 1 Chenxun Tai 1 Shuo Liu 1 Yi Cui 2 Bin Wang 3
Affiliations

Affiliations

  • 1 Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210000, China.
  • 2 Reproductive and Genetic Center of National Research Institute for Family Planning, Beijing, 100081, China. yicui22@126.com.
  • 3 Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210000, China. wangbin022800@126.com.
  • # Contributed equally.
Abstract

Objectives: To investigate the safety for clinic use and therapeutic effects of basic Fibroblast Growth Factor (bFGF)-overexpressing human umbilical cord-derived mesenchymal stem cells (HUCMSCs) in mice with completely transected spinal cord injury (SCI).

Methods: Stable bFGF-overexpressing HUCMSCs clones were established by electrotransfection and then subjected to systematic safety evaluations. Then, bFGF-overexpressing and control HUCMSCs were used to treat mice with completely transected SCI by tail intravenous injection. Therapeutic outcomes were then investigated, including functional recovery of locomotion, histological structures, nerve regeneration, and recovery mechanisms.

Results: Stable bFGF-overexpressing HUCMSCs met the standards and safety of MSCs for clinic use. In the mouse SCI model, stable bFGF-overexpressing HUCMSCs markedly improved therapeutic outcomes such as reducing glial scar formation, improving nerve regeneration and proliferation of endogenous neural stem cells (NSCs), and increasing locomotion functional recovery of posterior limbs compared with the control HUCMSCs group. Furthermore, bFGF-overexpressing HUCMSCs promoted the proliferation and neuronal differentiation of NSCs in vitro through the PI3K-Akt-GSK-3β pathway.

Conclusion: bFGF-overexpressing HUCMSCs meet the requirements of clinical MSCs and improve evident therapeutic outcomes of mouse SCI treatment, which firmly supports the safety and efficacy of gene-modified MSCs for clinical application.

Keywords

Basic fibroblast growth factor; Gene modification; Mesenchymal stem cells; Spinal cord injury.

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