PMID- 34419172
OWN - NLM
STAT- MEDLINE
DCOM- 20210825
LR  - 20210826
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 12
IP  - 1
DP  - 2021 Aug 21
TI  - 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-3beta signaling pathway.
PG  - 468
LID - 10.1186/s13287-021-02537-w [doi]
LID - 468
AB  - 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-3beta 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.
CI  - (c) 2021. The Author(s).
FAU - Huang, Feifei
AU  - Huang F
AD  - Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing 
      University Medical School, Nanjing, 210000, China.
FAU - Gao, Tianyun
AU  - Gao T
AD  - Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing 
      University Medical School, Nanjing, 210000, China.
FAU - Wang, Wenqing
AU  - Wang W
AD  - Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing 
      University Medical School, Nanjing, 210000, China.
FAU - Wang, Liudi
AU  - Wang L
AD  - Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing 
      University Medical School, Nanjing, 210000, China.
FAU - Xie, Yuanyuan
AU  - Xie Y
AD  - Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing 
      University Medical School, Nanjing, 210000, China.
FAU - Tai, Chenxun
AU  - Tai C
AD  - Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing 
      University Medical School, Nanjing, 210000, China.
FAU - Liu, Shuo
AU  - Liu S
AD  - Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing 
      University Medical School, Nanjing, 210000, China.
FAU - Cui, Yi
AU  - Cui Y
AD  - Reproductive and Genetic Center of National Research Institute for Family 
      Planning, Beijing, 100081, China. yicui22@126.com.
FAU - Wang, Bin
AU  - Wang B
AUID- ORCID: 0000-0003-3981-8849
AD  - Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing 
      University Medical School, Nanjing, 210000, China. wangbin022800@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210821
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cell Proliferation
MH  - Fibroblast Growth Factor 2/genetics
MH  - Glycogen Synthase Kinase 3 beta/genetics
MH  - Humans
MH  - *Mesenchymal Stem Cells
MH  - Mice
MH  - *Neural Stem Cells
MH  - Phosphatidylinositol 3-Kinases/genetics
MH  - Proto-Oncogene Proteins c-akt/genetics
MH  - Signal Transduction
MH  - *Spinal Cord Injuries/genetics/therapy
MH  - Umbilical Cord
PMC - PMC8379754
OTO - NOTNLM
OT  - Basic fibroblast growth factor
OT  - Gene modification
OT  - Mesenchymal stem cells
OT  - Spinal cord injury
COIS- The authors declare that they have no competing interests.
EDAT- 2021/08/23 06:00
MHDA- 2021/08/26 06:00
PMCR- 2021/08/21
CRDT- 2021/08/22 20:33
PHST- 2021/06/08 00:00 [received]
PHST- 2021/08/03 00:00 [accepted]
PHST- 2021/08/22 20:33 [entrez]
PHST- 2021/08/23 06:00 [pubmed]
PHST- 2021/08/26 06:00 [medline]
PHST- 2021/08/21 00:00 [pmc-release]
AID - 10.1186/s13287-021-02537-w [pii]
AID - 2537 [pii]
AID - 10.1186/s13287-021-02537-w [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2021 Aug 21;12(1):468. doi: 10.1186/s13287-021-02537-w.