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Post-ischemic Intravenous Administration of Allogeneic Dental Pulp-Derived Neurosphere Cells Ameliorated Outcomes of Severe Forebrain Ischemia in Rats

  • Translational Research
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Abstract

Background

Transplantation of bone marrow or adipose-derived mesenchymal stem cells (MSCs) for various neurological disorders has yielded promising results in models of focal cerebral ischemia. Dental pulp stem cells (DPSCs) are a type of MSC. In serum-free culture, they can form neurospheres that contain nestin-positive neuronal progenitor cells. We hypothesized that transplantation of dental pulp-derived neurosphere cells would ameliorate outcomes of global cerebral ischemia, the pathophysiology of which is known to resist conventional treatments. We also hypothesized that transplantation of dental pulp-derived cells would provide some neuroprotection in this pathology due to the presence of DPSCs.

Methods

Using adult rats, ischemia was induced by two-vessel occlusion of both carotid arteries in combination with systemic hypotension. Allogeneic dental pulp cells from juvenile rats were cultured in advance in serum-free medium to obtain neurospheres. Dental pulp-derived neurosphere cells or dental pulp-derived cells were intravenously administered at 3 h after ischemic insult, with normal saline as a control. Animals were observed for 14 days after ischemia. Neurological outcome was assessed using the water-maze test and neuromotor test. Histological outcome was measured by counting the percentage of dead neurons in the hippocampal CA1 and CA3 regions.

Results

Transplantation of both dental pulp-derived neurosphere cells and dental pulp-derived cells significantly improved survival rate and water-maze test results. Neurosphere cell transplantation was related to significantly better neuromotor test and histological outcomes, as indicated by the reduced percentage of dead neurons in CA1.

Conclusions

Transplantation of dental pulp-derived neurosphere cells ameliorated outcomes of global cerebral ischemia. It was also demonstrated that dental pulp-derived cell administration provided some neuroprotection.

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Funding

This study was supported by the “High-Tech Research Center” Project for Private Universities, with a matching fund subsidy from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Department of Anesthesiology, Yamagata University School of Medicine, Yamagata, Japan

    Airi Kumasaka

  2. Department of Dental Anesthesiology, School of Dentistry, Health Sciences University of Hokkaido, Kanazawa, Japan

    Kaoru Kanazawa, Hanako Ohke & Yoshihide Miura

  3. School of Human Science and Environment, University of Hyogo, Kobe, Japan

    Ikumi Miura

Authors
  1. Airi Kumasaka
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  2. Kaoru Kanazawa
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  3. Hanako Ohke
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  4. Ikumi Miura
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Correspondence to Yoshihide Miura.

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The authors declare that they have no conflict of interest.

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All applicable institutional and/or national guidelines for the care and use of animals were followed.

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Kumasaka, A., Kanazawa, K., Ohke, H. et al. Post-ischemic Intravenous Administration of Allogeneic Dental Pulp-Derived Neurosphere Cells Ameliorated Outcomes of Severe Forebrain Ischemia in Rats. Neurocrit Care 26, 133–142 (2017). https://doi.org/10.1007/s12028-016-0304-4

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