Human dental pulp-derived stem cells protect against hypoxic-ischemic brain injury in neonatal mice
Mari Yamagata1, Akihito Yamamoto, Eisuke Kako
1Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Insights
Stem cells from human exfoliated deciduous teeth (SHED) show therapeutic potential for neonatal brain injury caused by hypoxia-ischemia (HI). SHED transplantation and their conditioned medium improved neurological function and reduced tissue loss in a mouse model.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Neonatal Brain Injury
Background:
- Perinatal hypoxia-ischemia (HI) leads to significant neurological deficits and mortality.
- Current treatments for HI brain injury remain ineffective.
- Investigating novel therapeutic strategies is crucial.
Purpose of the Study:
- To evaluate the therapeutic efficacy of stem cells from human exfoliated deciduous teeth (SHED) for neonatal HI brain injury.
- To assess the impact of SHED transplantation and their conditioned medium on neurological and pathophysiological recovery.
Main Methods:
- Neonatal mice (postnatal day 5) underwent unilateral HI induction.
- SHED, fibroblasts, or SHED-conditioned medium were injected into the injured brain 24 hours post-HI.
- Neurological function, tissue loss, apoptosis, and cytokine expression were evaluated.
Main Results:
- SHED transplantation significantly reduced HI-induced brain tissue loss and improved neurological function.
- SHED improved survival rates in HI mice and modulated inflammatory responses.
- SHED-conditioned medium also demonstrated significant neuroprotective effects, reducing apoptosis and tissue loss.
Conclusions:
- SHED transplantation promotes remarkable neurological and pathophysiological recovery in HI-injured brains.
- Paracrine factors from SHED create a neuroprotective microenvironment.
- SHED grafts and conditioned medium represent a promising novel therapy for HI brain injury.
Background And Purpose:
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.
