A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Intravenously delivered multilineage-differentiating stress enduring cells dampen excessive glutamate metabolism and microglial activation in experimental perinatal hypoxic ischemic encephalopathy
Tekijät: Toshihiko Suzuki, Yoshiaki Sato, Yoshihiro Kushida, Masahiro Tsuji, Shohei Wakao, Kazuto Ueda, Kenji Imai, Yukako Iitani, Shinobu Shimizu, Hideki Hida, Takashi Temma, Shigeyoshi Saito, Hidehiro Iida, Masaaki Mizuno, Yoshiyuki Takahashi, Mari Dezawa, Cesar V Borlongan, Masahiro Hayakawa
Kustantaja: SAGE
Julkaisuvuosi: 2020
Journal: Journal of Cerebral Blood Flow and Metabolism
eISSN: 1559-7016
DOI: https://doi.org/10.1177/0271678X20972656
Perinatal
hypoxic ischaemic encephalopathy (HIE) results in serious neurological
dysfunction and mortality. Muse cells have unique features represented by non-tumorigenicity,
triploblastic-differentiation ability, specific homing to damaged site by
sphingosine-1-phosphate (S1P)-S1P receptor 2 system, and replacement of
damaged/lost cells by in vivo-differentiation into tissue-constituent cells.
They are already applied to clinical trials including stroke by intravenous
drip of donor-derived Muse cell preparation. We investigated the therapeutic
effect of intravenously administered human-Muse cells on rat HIE model.
Methods
Seven-day-old
rats underwent ligation of the left carotid artery and were exposed to 8%
oxygen for 60 min. 1 × 104 of human-Muse and -non-Muse cells, collected
from human bone marrow-MSCs as SSEA-3(+) and (-), respectively, or saline
(vehicle) were administered to rats via the right external jugular vein 72 h
after the insult without immunosuppression. Neurological and pathophysiological
analysis were done.
Results
By using
human-specific probe, intravenously injected human-Muse cells were shown to
distributed mainly to the injured brain at 2 and 4 weeks, and they expressed
neuronal and glial markers until 6 months. In contrast, non-Muse cells, mostly
detected in the lung and not in the brain at 2 weeks, became undetectable even
from the lung at 4 weeks. Magnetic resonance spectroscopy and positron emission
tomography demonstrated that Muse cells dampened brain metabolites
released following hypoxic ischemic damage and suppressed microglial
activity. In the behavioural tests performed at 4 weeks1 and 5 months, the Muse
group showed remarkable improvement in motor impairment, cognitive dysfunction
and behavioural abnormalities (hyperactivity), compared to the vehicle and
non-Muse groups with statistical significance.
Conclusions
Intravenous injection of Muse cells may deliver
beneficial effect on HIE and be worth investigating further as a potential
treatment for this condition.
