PMID- 29568282
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1664-2295 (Print)
IS  - 1664-2295 (Electronic)
IS  - 1664-2295 (Linking)
VI  - 9
DP  - 2018
TI  - Dose-Dependent Effect of Intravenous Administration of Human Umbilical 
      Cord-Derived Mesenchymal Stem Cells in Neonatal Stroke Mice.
PG  - 133
LID - 10.3389/fneur.2018.00133 [doi]
LID - 133
AB  - Neonatal brain injury induced by stroke causes significant disability, including 
      cerebral palsy, and there is no effective therapy for stroke. Recently, 
      mesenchymal stem cells (MSCs) have emerged as a promising tool for stem 
      cell-based therapies. In this study, we examined the safety and efficacy of 
      intravenously administered human umbilical cord-derived MSCs (UC-MSCs) in 
      neonatal stroke mice. Pups underwent permanent middle cerebral artery occlusion 
      at postnatal day 12 (P12), and low-dose (1 x 10(4)) or high-dose (1 x 10(5)) 
      UC-MSCs were administered intravenously 48 h after the insult (P14). To evaluate 
      the effect of the UC-MSC treatment, neurological behavior and cerebral blood flow 
      were measured, and neuroanatomical analysis was performed at P28. To investigate 
      the mechanisms of intravenously injected UC-MSCs, systemic blood flowmetry, in 
      vivo imaging and human brain-derived neurotrophic factor (BDNF) measurements were 
      performed. Functional disability was significantly improved in the high-dose 
      UC-MSC group when compared with the vehicle group, but cerebral blood flow and 
      cerebral hemispheric volume were not restored by UC-MSC therapy. The level of 
      exogenous human BDNF was elevated only in the cerebrospinal fluid of one pup 24 h 
      after UC-MSC injection, and in vivo imaging revealed that most UC-MSCs were 
      trapped in the lungs and disappeared in a week without migration toward the brain 
      or other organs. We found that systemic blood flow was stable over the 10 min 
      after cell administration and that there were no differences in mortality among 
      the groups. Immunohistopathological assessment showed that the percent area of 
      Iba1-positive staining in the peri-infarct cortex was significantly reduced with 
      the high-dose UC-MSC treatment compared with the vehicle treatment. These results 
      suggest that intravenous administration of UC-MSCs is safe for a mouse model of 
      neonatal stroke and improves dysfunction after middle cerebral artery occlusion 
      by modulating the microglial reaction in the peri-infarct cortex.
FAU - Tanaka, Emi
AU  - Tanaka E
AD  - Department of Regenerative Medicine and Tissue Engineering, National Cerebral and 
      Cardiovascular Center, Suita, Japan.
AD  - Department of Pediatrics, Osaka City University Graduate School of Medicine, 
      Osaka, Japan.
FAU - Ogawa, Yuko
AU  - Ogawa Y
AD  - Department of Regenerative Medicine and Tissue Engineering, National Cerebral and 
      Cardiovascular Center, Suita, Japan.
FAU - Mukai, Takeo
AU  - Mukai T
AD  - Department of Cell Processing and Transfusion, Institute of Medical Science, The 
      University of Tokyo, Tokyo, Japan.
FAU - Sato, Yoshiaki
AU  - Sato Y
AD  - Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University 
      Hospital, Nagoya, Japan.
FAU - Hamazaki, Takashi
AU  - Hamazaki T
AD  - Department of Pediatrics, Osaka City University Graduate School of Medicine, 
      Osaka, Japan.
FAU - Nagamura-Inoue, Tokiko
AU  - Nagamura-Inoue T
AD  - Department of Cell Processing and Transfusion, Institute of Medical Science, The 
      University of Tokyo, Tokyo, Japan.
FAU - Harada-Shiba, Mariko
AU  - Harada-Shiba M
AD  - Department of Regenerative Medicine and Tissue Engineering, National Cerebral and 
      Cardiovascular Center, Suita, Japan.
FAU - Shintaku, Haruo
AU  - Shintaku H
AD  - Department of Pediatrics, Osaka City University Graduate School of Medicine, 
      Osaka, Japan.
FAU - Tsuji, Masahiro
AU  - Tsuji M
AD  - Department of Regenerative Medicine and Tissue Engineering, National Cerebral and 
      Cardiovascular Center, Suita, Japan.
LA  - eng
PT  - Journal Article
DEP - 20180308
PL  - Switzerland
TA  - Front Neurol
JT  - Frontiers in neurology
JID - 101546899
PMC - PMC5852073
OTO - NOTNLM
OT  - intravenous administration
OT  - mesenchymal stem cell
OT  - neonatal brain injury
OT  - neonatal stroke
OT  - umbilical cord-derived mesenchymal stem cell
EDAT- 2018/03/24 06:00
MHDA- 2018/03/24 06:01
PMCR- 2018/03/08
CRDT- 2018/03/24 06:00
PHST- 2017/12/28 00:00 [received]
PHST- 2018/02/22 00:00 [accepted]
PHST- 2018/03/24 06:00 [entrez]
PHST- 2018/03/24 06:00 [pubmed]
PHST- 2018/03/24 06:01 [medline]
PHST- 2018/03/08 00:00 [pmc-release]
AID - 10.3389/fneur.2018.00133 [doi]
PST - epublish
SO  - Front Neurol. 2018 Mar 8;9:133. doi: 10.3389/fneur.2018.00133. eCollection 2018.