4.7 Article

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

期刊

STEM CELL RESEARCH & THERAPY
卷 12, 期 1, 页码 -

出版社

BMC
DOI: 10.1186/s13287-021-02537-w

关键词

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

资金

  1. National Key Research and Development Program of China [2017YFA0104304]
  2. National Natural Science Foundation of China (NSFC) [81571213, 82070459, 82071403, 81800583]
  3. Key Project of Jiangsu Province [BE2020765]
  4. Nanjing Medical Science and Technique Development Foundation [QRX17006, QRX17057, ZKX20016]
  5. Jiangsu Provincial Plan for Mass Entrepreneurship and Innovation
  6. Project of Modern Hospital Management and Development Institute, Nanjing University/Aid project of Nanjing Drum Tower Hospital Health, Education & Research Foundation [NDYG2020030]
  7. Nanjing Department of Health [201803024]

向作者/读者索取更多资源

The study showed that bFGF-overexpressing HUCMSCs met clinical safety standards and significantly improved therapeutic outcomes in a mouse SCI model. This included reducing glial scar formation, enhancing nerve regeneration and NSC proliferation, and improving locomotion function recovery. Additionally, bFGF-overexpressing HUCMSCs promoted NSC proliferation and neuronal differentiation in vitro through the PI3K-Akt-GSK-3 beta pathway, supporting the safety and efficacy of gene-modified MSCs for clinical use.
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-3 beta 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.

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