PMID- 24172866
OWN - NLM
STAT- MEDLINE
DCOM- 20141103
LR  - 20220331
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 22
IP  - 3
DP  - 2014 Mar
TI  - Therapeutic potential of genetically modified mesenchymal stem cells after 
      neonatal hypoxic-ischemic brain damage.
PG  - 645-654
LID - S1525-0016(16)31188-1 [pii]
LID - 10.1038/mt.2013.260 [doi]
AB  - Mesenchymal stem cells (MSCs) have been shown to improve outcomes after neonatal 
      hypoxic-ischemic (HI) brain injury possibly by secretion of growth factors 
      stimulating repair processes. We investigated whether MSCs, modified to secrete 
      specific growth factors, can further enhance recovery. Using an in vitro assay, 
      we show that MSC-secreting brain derived neurotrophic factor (BDNF), epidermal 
      growth factor-like 7 (EGFL7), persephin (PSP), or sonic hedgehog (SHH) regulate 
      proliferation and differentiation of neural stem cells. Moreover, mice that 
      received an intranasal application of 100,000 MSC-BDNF showed significantly 
      improved outcomes as demonstrated by improved motor function and decreased lesion 
      volume compared with mice treated with empty vector (EV) MSCs. Treatment with 
      MSC-EGFL7 improved motor function but had no effect on lesion size. Treatment 
      with MSC-PSP or MSC-SHH neither improved outcome nor reduced lesion size in 
      comparison with MSC-EV-treated mice. Moreover, mice treated with MSC-SHH showed 
      even decreased functional outcomes when compared with those treated with MSC-EV. 
      Treatment with MSC-BDNF induced cell proliferation in the ischemic hemisphere 
      lasting at least 18 days after MSC administration, whereas treatment with MSC-EV 
      did not. These data suggest that gene-modified cell therapy might be a useful 
      approach to consider for treatment of neonatal HI brain damage. However, care 
      must be taken when selecting the agent to overexpress.
FAU - van Velthoven, Cindy Tj
AU  - van Velthoven CT
AD  - Laboratory of Neuroimmunology and Developmental Origins of Disease, University 
      Medical Center Utrecht, Utrecht, The Netherlands.
FAU - Braccioli, Luca
AU  - Braccioli L
AD  - Laboratory of Neuroimmunology and Developmental Origins of Disease, University 
      Medical Center Utrecht, Utrecht, The Netherlands.
FAU - Willemen, Hanneke Ldm
AU  - Willemen HL
AD  - Laboratory of Neuroimmunology and Developmental Origins of Disease, University 
      Medical Center Utrecht, Utrecht, The Netherlands.
FAU - Kavelaars, Annemieke
AU  - Kavelaars A
AD  - Department of Symptom Research, University of Texas, MD Anderson Cancer Center, 
      Houston, Texas, USA.
FAU - Heijnen, Cobi J
AU  - Heijnen CJ
AD  - Laboratory of Neuroimmunology and Developmental Origins of Disease, University 
      Medical Center Utrecht, Utrecht, The Netherlands; Department of Symptom Research, 
      University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. Electronic 
      address: CJHeijnen@mdanderson.org.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131031
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Egfl7 protein, mouse)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Proteins)
RN  - 0 (Shh protein, mouse)
RN  - 0 (persephin)
SB  - IM
MH  - Adenoviridae/*genetics
MH  - Administration, Intranasal
MH  - Animals
MH  - Animals, Newborn
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - Calcium-Binding Proteins
MH  - Cell Differentiation
MH  - Cell Proliferation
MH  - EGF Family of Proteins
MH  - Genetic Vectors/*administration & dosage/therapeutic use
MH  - Hedgehog Proteins/genetics/metabolism
MH  - Hypoxia-Ischemia, Brain/pathology/*therapy
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nerve Tissue Proteins/genetics/metabolism
MH  - Neural Stem Cells/*metabolism
MH  - Oligodendroglia/metabolism
MH  - Proteins/genetics/metabolism
MH  - Transduction, Genetic
MH  - Treatment Outcome
PMC - PMC3944339
EDAT- 2013/11/01 06:00
MHDA- 2014/11/05 06:00
PMCR- 2015/03/01
CRDT- 2013/11/01 06:00
PHST- 2013/06/12 00:00 [received]
PHST- 2013/10/10 00:00 [accepted]
PHST- 2013/11/01 06:00 [entrez]
PHST- 2013/11/01 06:00 [pubmed]
PHST- 2014/11/05 06:00 [medline]
PHST- 2015/03/01 00:00 [pmc-release]
AID - S1525-0016(16)31188-1 [pii]
AID - 10.1038/mt.2013.260 [doi]
PST - ppublish
SO  - Mol Ther. 2014 Mar;22(3):645-654. doi: 10.1038/mt.2013.260. Epub 2013 Oct 31.