PMID- 31296795
OWN - NLM
STAT- MEDLINE
DCOM- 20200824
LR  - 20200824
IS  - 1741-2552 (Electronic)
IS  - 1741-2552 (Linking)
VI  - 16
IP  - 5
DP  - 2019 Aug 12
TI  - KLF7 overexpression in bone marrow stromal stem cells graft transplantation 
      promotes sciatic nerve regeneration.
PG  - 056011
LID - 10.1088/1741-2552/ab3188 [doi]
AB  - OBJECTIVE: Our previous study demonstrated that the transcription factor, 
      Kruppel-like Factor 7 (KLF7), stimulates axon regeneration following peripheral 
      nerve injury. In the present study, we used a gene therapy approach to 
      overexpress KLF7 in bone marrow-derived stem/stromal cells (BMSCs) as support 
      cells, combined with acellular nerve allografts (ANAs) and determined the 
      potential therapeutic efficacy of a KLF7-transfected BMSC nerve graft 
      transplantation in a rodent model for sciatic nerve injury and repair. APPROACH: 
      We efficiently transfected BMSCs with adeno-associated virus (AAV)-KLF7, which 
      were then seeded in ANAs for bridging sciatic nerve defects. MAIN RESULTS: KLF7 
      overexpression promotes proliferation, survival, and Schwann-like cell 
      differentiation of BMSCs in vitro. In vivo, KLF7 overexpression promotes 
      transplanted BMSCs survival and myelinated fiber regeneration in regenerating 
      ANAs; however, KLF7 did not improve Schwann-like cell differentiation of BMSCs 
      within in the nerve grafts. KLF7-BMSCs significantly upregulated expression and 
      secretion of neurotrophic factors by BMSCs, including nerve growth factor, 
      ciliary neurotrophic factor, brain-derived neurotrophic factor, and glial cell 
      line-derived neurotrophic factor in regenerating ANA. KLF7-BMSCs also improved 
      motor axon regeneration, and subsequent neuromuscular innervation and prevention 
      of muscle atrophy. These benefits were associated with increased motor functional 
      recovery of regenerating ANAs. SIGNIFICANCE: Our findings suggest that KLF7-BMSCs 
      promoted peripheral nerve axon regeneration and myelination, and ultimately, 
      motor functional recovery. The mechanism of KLF7 action may be related to its 
      ability to enhance transplanted BMSCs survival and secrete neurotrophic factors 
      rather than Schwann-like cell differentiation. This study provides novel 
      foundational data connecting the benefits of KLF7 in neural injury and repair to 
      BMSC biology and function, and demonstrates a potential combination approach for 
      the treatment of injured peripheral nerve via nerve graft transplant.
FAU - Li, Wen-Yuan
AU  - Li WY
AD  - Institute of Neural Tissue Engineering, Mudanjiang College of Medicine, 
      Mudanjiang 157011, People's Republic of China.
FAU - Zhu, Guan-Yu
AU  - Zhu GY
FAU - Yue, Wen-Jiang
AU  - Yue WJ
FAU - Sun, Guang-Da
AU  - Sun GD
FAU - Zhu, Xiao-Feng
AU  - Zhu XF
FAU - Wang, Ying
AU  - Wang Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190812
PL  - England
TA  - J Neural Eng
JT  - Journal of neural engineering
JID - 101217933
RN  - 0 (Klf7 protein, mouse)
RN  - 0 (Kruppel-Like Transcription Factors)
SB  - IM
MH  - Animals
MH  - Bone Marrow Transplantation/*methods
MH  - Cell Differentiation/physiology
MH  - Cells, Cultured
MH  - Female
MH  - Gene Expression
MH  - Kruppel-Like Transcription Factors/*biosynthesis/genetics
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation/*methods
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred ICR
MH  - Nerve Regeneration/*physiology
MH  - Sciatic Nerve/*metabolism/pathology
MH  - Sciatic Neuropathy/*metabolism/pathology/therapy
EDAT- 2019/07/13 06:00
MHDA- 2020/08/25 06:00
CRDT- 2019/07/13 06:00
PHST- 2019/07/13 06:00 [pubmed]
PHST- 2020/08/25 06:00 [medline]
PHST- 2019/07/13 06:00 [entrez]
AID - 10.1088/1741-2552/ab3188 [doi]
PST - epublish
SO  - J Neural Eng. 2019 Aug 12;16(5):056011. doi: 10.1088/1741-2552/ab3188.