title: Human dental pulp-derived stem cells protect against hypoxic-ischemic brain injury in neonatal mice.
abstract: OBJECTIVE
  Perinatal hypoxia-ischemia (HI) has high rates of neurological deficits and mortality. So far, no effective treatment for HI brain injury has been developed. In this study, we investigated the therapeutic effects of stem cells from human exfoliated deciduous teeth (SHED) for the treatment of neonatal HI brain injury.
  
  
  METHODS
  Unilateral HI was induced in postnatal day 5 (P5) mice. Twenty-four hours later, SHED, human skin fibroblasts, or serum-free conditioned medium derived from these cells was injected into the injured brain. The effects of cell transplantation or conditioned medium injection on the animals' neurological and pathophysiological recovery were evaluated.
  
  
  RESULTS
  Transplanted SHED, but not fibroblasts, significantly reduced the HI-induced brain-tissue loss and improved neurological function. SHED also improved the survival of the HI mice. The engrafted SHED rarely differentiated into neural lineages; however, their transplantation inhibited the expression of proinflammatory cytokines, increased the expression of anti-inflammatory ones, and significantly reduced apoptosis. Notably, the intracerebral administration of SHED-conditioned medium also significantly improved the neurological outcome, inhibited apoptosis, and reduced tissue loss.
  
  
  CONCLUSIONS
  SHED transplantation into the HI-injured brain resulted in remarkable neurological and pathophysiological recovery. Our findings indicate that paracrine factors derived from SHED support a neuroprotective microenvironment in the HI brain. SHED graft and SHED-conditioned medium may provide a novel neuroprotective therapy for HI.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Yamagata
authors.forename: Akihito
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Eisuke
authors.initials: E
authors.lastname: Kako
authors.forename: Naoko
authors.initials: N
authors.lastname: Kaneko
authors.forename: Kohki
authors.initials: K
authors.lastname: Matsubara
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sakai
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Sawamoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Ueda
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000473:pathology / Q000601:surgery*; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology* / Q000637:transplantation*; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000601:surgery*; D051379:Mice; D033581:Stem Cell Transplantation / Q000379:methods*