PMID- 32403417
OWN - NLM
STAT- MEDLINE
DCOM- 20210224
LR  - 20210224
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 9
IP  - 5
DP  - 2020 May 11
TI  - TNF-alpha Pretreatment Improves the Survival and Function of Transplanted Human 
      Neural Progenitor Cells Following Hypoxic-Ischemic Brain Injury.
LID - 10.3390/cells9051195 [doi]
LID - 1195
AB  - Neural progenitor cells (NPCs) therapy offers great promise in hypoxic-ischemic 
      (HI) brain injury. However, the poor survival of implanted NPCs in the HI host 
      environment limits their therapeutic effects. Tumor necrosis factor-alpha (TNF-alpha) 
      is a pleiotropic cytokine that is induced in response to a variety of 
      pathological processes including inflammation and immunity. On the other hand, 
      TNF-alpha has protective effects on cell apoptosis and death and affects the 
      differentiation, proliferation, and survival of neural stem/progenitor cells in 
      the brain. The present study investigated whether TNF-alpha pretreatment on human 
      NPCs (hNPCs) enhances the effectiveness of cell transplantation therapy under 
      ischemic brain. Fetal brain tissue-derived hNPCs were pretreated with TNF-alpha 
      before being used in vitro experiments or transplantation. TNF-alpha significantly 
      increased expression of cIAP2, and the use of short hairpin RNA-mediated 
      knockdown of cIAP2 demonstrated that cIAP2 protected hNPCs against HI-induced 
      cytotoxicity. In addition, pretreatment of hNPCs with TNF-alpha mediated 
      neuroprotection by altering microglia polarization via increased expression of 
      CX3CL1 and by enhancing expression of neurotrophic factors. Furthermore, 
      transplantation of TNF-alpha-treated hNPCs reduced infarct volume and improved 
      neurological functions in comparison with non-pretreated hNPCs or vehicle. These 
      findings show that TNF-alpha pretreatment, which protects hNPCs from HI-injured 
      brain-induced apoptosis and increases neuroprotection, is a simple and safe 
      approach to improve the survival of transplanted hNPCs and the therapeutic 
      efficacy of hNPCs in HI brain injury.
FAU - Kim, Miri
AU  - Kim M
AD  - Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 
      Seoul 03722, Korea.
FAU - Jung, Kwangsoo
AU  - Jung K
AD  - Department of Pediatrics, Severance Children's Hospital, Yonsei University 
      College of Medicine, Seoul 03722, Korea.
FAU - Ko, Younhee
AU  - Ko Y
AD  - Division of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin 
      17035, Korea.
FAU - Kim, Il-Sun
AU  - Kim IS
AD  - Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 
      Seoul 03722, Korea.
FAU - Hwang, Kyujin
AU  - Hwang K
AD  - Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 
      Seoul 03722, Korea.
AD  - Brain Korea 21 Plus Project for Medical Science, Yonsei University College of 
      Medicine, Seoul 03722, Korea.
FAU - Jang, Jae-Hyung
AU  - Jang JH
AD  - Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 
      03722, Korea.
FAU - Shin, Jeong Eun
AU  - Shin JE
AUID- ORCID: 0000-0002-4376-8541
AD  - Department of Pediatrics, Severance Children's Hospital, Yonsei University 
      College of Medicine, Seoul 03722, Korea.
FAU - Park, Kook In
AU  - Park KI
AD  - Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 
      Seoul 03722, Korea.
AD  - Department of Pediatrics, Severance Children's Hospital, Yonsei University 
      College of Medicine, Seoul 03722, Korea.
AD  - Brain Korea 21 Plus Project for Medical Science, Yonsei University College of 
      Medicine, Seoul 03722, Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200511
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Chemokine CX3CL1)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - EC 2.3.2.27 (Baculoviral IAP Repeat-Containing 3 Protein)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Animals
MH  - Baculoviral IAP Repeat-Containing 3 Protein/metabolism
MH  - Behavior, Animal/drug effects
MH  - Brain Injuries/complications/pathology/*therapy
MH  - Caspase 3/metabolism
MH  - Cell Line
MH  - Cell Polarity/drug effects
MH  - Cell Survival/drug effects
MH  - Chemokine CX3CL1/metabolism
MH  - Culture Media, Conditioned/pharmacology
MH  - Glutamic Acid/toxicity
MH  - Humans
MH  - Hypoxia-Ischemia, Brain/complications/pathology/*therapy
MH  - Mice, Inbred ICR
MH  - Microglia/drug effects/metabolism/pathology
MH  - Nerve Growth Factors/metabolism
MH  - Neural Stem Cells/drug effects/pathology/*transplantation
MH  - Neurons/drug effects/metabolism/pathology
MH  - Neuroprotection/drug effects
MH  - Phenotype
MH  - Stress, Physiological/drug effects
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Up-Regulation/drug effects
PMC - PMC7291333
OTO - NOTNLM
OT  - CX3CL1
OT  - cell survival
OT  - cellular inhibitor of apoptosis 2
OT  - human neural progenitor cells
OT  - hypoxic-ischemic brain injury
OT  - tumor necrosis factor-alpha
COIS- The authors declare no conflict of interest.
EDAT- 2020/05/15 06:00
MHDA- 2021/02/25 06:00
PMCR- 2020/05/01
CRDT- 2020/05/15 06:00
PHST- 2020/03/09 00:00 [received]
PHST- 2020/04/28 00:00 [revised]
PHST- 2020/05/07 00:00 [accepted]
PHST- 2020/05/15 06:00 [entrez]
PHST- 2020/05/15 06:00 [pubmed]
PHST- 2021/02/25 06:00 [medline]
PHST- 2020/05/01 00:00 [pmc-release]
AID - cells9051195 [pii]
AID - cells-09-01195 [pii]
AID - 10.3390/cells9051195 [doi]
PST - epublish
SO  - Cells. 2020 May 11;9(5):1195. doi: 10.3390/cells9051195.