Faculty Profiles - SAKAI Kiyoshi

Papers - SAKAI Kiyoshi

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Ablation of Coactivator Med1 Switches the Cell Fate of Dental Epithelia to That Generating Hair Reviewed International coauthorship International journal

Keigo Yoshizaki, Lizhi Hu, Thai Nguyen, Kiyoshi Sakai, Bing He, Chak Fong, Yoshihiko Yamada, Daniel D. Bikle, Yuko Oda

PLOS ONE Vol. 9 ( 6 ) 2014.6

Language：English Publishing type：Research paper (scientific journal) Publisher：PUBLIC LIBRARY SCIENCE

Cell fates are determined by specific transcriptional programs. Here we provide evidence that the transcriptional coactivator, Mediator 1 (Med1), is essential for the cell fate determination of ectodermal epithelia. Conditional deletion of Med1 in vivo converted dental epithelia into epidermal epithelia, causing defects in enamel organ development while promoting hair formation in the incisors. We identified multiple processes by which hairs are generated in Med1 deficient incisors: 1) dental epithelial stem cells lacking Med 1 fail to commit to the dental lineage, 2) Sox2-expressing stem cells extend into the differentiation zone and remain multi-potent due to reduced Notch1 signaling, and 3) epidermal fate is induced by calcium as demonstrated in dental epithelial cell cultures. These results demonstrate that Med1 is a master regulator in adult stem cells to govern epithelial cell fate.

DOI： 10.1371/journal.pone.0099991

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Multifaceted neuro-regenerative activities of human dental pulp stem cells for functional recovery after spinal cord injury Reviewed International journal

Akihito Yamamoto, Kiyoshi Sakai, Kohki Matsubara, Fumiya Kano, Minoru Ueda

NEUROSCIENCE RESEARCH Vol. 78 page： 16 - 20 2014.1

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

Spinal cord injury (SCI) often leads to persistent functional deficits due to the loss of neurons and glia and to limited axonal regeneration after such injury. Recently, three independent groups have reported marked recovery of hindlimb locomotor function after the transplantation of human adult dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHEDs) into rats or mice with acute, sub-acute or chronic SCI. This review summarizes the primary characteristics of human dental pulp stem cells and their therapeutic benefits for treating SCI. Experimental data from multiple preclinical studies suggest that pulp stem cells may promote functional recovery after SCI through multifaceted neuro-regenerative activities. (C) 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

DOI： 10.1016/j.neures.2013.10.010

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Analysis of the neuroregenerative activities of mesenchymal stem cells in functional recovery after rat spinal cord injury Reviewed International journal

A. Yamamoto, K. Matsubara, F. Kano, K. Sakai

Methods in Molecular Biology page： 321-328 2014

Analysis of the Neuroregenerative Activities of Mesenchymal Stem Cells in Functional Recovery after Rat Spinal Cord Injury International journal

Yamamoto Akihito, Matsubara Kohki, Kano Fumiya, Sakai Kiyoshi

ANIMAL MODELS FOR STEM CELL THERAPY Vol. 1213 page： 321 - 328 2014

Multifaceted Neuro-Regenerative Activities of Human Dental Pulp Stem Cells for Functional Recovery after Spinal Cord Injury International journal

Yamamoto Akihito, Matsubara Kohki, Sakai Kiyoshi, Kano Fumiya, Ueda Minoru

NEW TRENDS IN TISSUE ENGINEERING AND REGENERATIVE MEDICINE - OFFICIAL BOOK OF THE JAPANESE SOCIETY FOR REGENERATIVE MEDICINE page： 67 - 79 2014

Human Dental Pulp-Derived Stem Cells Protect Against Hypoxic-Ischemic Brain Injury in Neonatal Mice Reviewed International journal

Mari Yamagata, Akihito Yamamoto, Eisuke Kako, Naoko Kaneko, Kohki Matsubara, Kiyoshi Sakai, Kazunobu Sawamoto, Minoru Ueda

STROKE Vol. 44 ( 2 ) page： 551 - 554 2013.2

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

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. (Stroke. 2013;44:551-554.)

DOI： 10.1161/STROKEAHA.112.676759

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Human umbilical cord-derived mesenchymal stromal cells promote sensory recovery in a spinl cord injury rat model Reviewed International journal

S. Takikawa, A. Yamamoto, K. Sakai, R. Shohara, A. Iwase, F. Kikkawa, M. Ueda

Stem Cell Discovery page： 155-163 2013

Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms Reviewed International journal

Kiyoshi Sakai, Akihito Yamamoto, Kohki Matsubara, Shoko Nakamura, Mami Naruse, Mari Yamagata, Kazuma Sakamoto, Ryoji Tauchi, Norimitsu Wakao, Shiro Imagama, Hideharu Hibi, Kenji Kadomatsu, Naoki Ishiguro, Minoru Ueda

JOURNAL OF CLINICAL INVESTIGATION Vol. 122 ( 1 ) page： 80 - 90 2012.1

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：AMER SOC CLINICAL INVESTIGATION INC

Spinal cord injury (SCI) often leads to persistent functional deficits due to loss of neurons and glia and to limited axonal regeneration after injury. Here we report that transplantation of human dental pulp stem cells into the completely transected adult rat spinal cord resulted in marked recovery of hind limb locomotor functions. Transplantation of human bone marrow stromal cells or skin-derived fibroblasts led to substantially less recovery of locomotor function. The human dental pulp stem cells exhibited three major neuroregenerative activities. First, they inhibited the SCI-induced apoptosis of neurons, astrocytes, and oligodendrocytes, which improved the preservation of neuronal filaments and myelin sheaths. Second, they promoted the regeneration of transected axons by directly inhibiting multiple axon growth inhibitors, including chondroitin sulfate proteoglycan and myelin-associated glycoprotein, via paracrine mechanisms. Last, they replaced lost cells by differentiating into mature oligodendrocytes under the extreme conditions of SCI. Our data demonstrate that tooth-derived stem cells may provide therapeutic benefits for treating SCI through both cell-autonomous and paracrine neuroregenerative activities.

DOI： 10.1172/JCI59251

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Stability of a Locking Plate and Self-Drilling Screws as Orthodontic Skeletal Anchorage in the Maxilla: A Retrospective Study Reviewed International journal

Hidebaru Hibi, Kiyoshi Sakai, Tomoo Oda, Hisashi Hattori, Minoru Ueda, Masaru Sakai

JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY Vol. 68 ( 8 ) page： 1783 - 1787 2010.8

Language：English Publishing type：Research paper (scientific journal) Publisher：W B SAUNDERS CO-ELSEVIER INC

Purpose: The aim of this retrospective study was to determine the success rate of an orthodontic skeletal anchorage system consisting of a locking plate and 2 self-drilling screws to intrude the upper molars and detect factors that contribute to its stability.
Patients and Methods: The subjects were 32 orthodontic and generally healthy patients who had skeletal anchorage plates placed supraperiosteally and unilaterally or bilaterally. The anchorage plate was considered successful if the plate remained stable throughout the period of intrusion of the upper molar without any movement, persistent pain, or infection and was then retrieved without difficulty. The success rates of the anchorage plate were statistically analyzed on the basis of clinically categorized variables.
Results: The 32 patients comprised 6 male and 26 female individuals with ages ranging from 11.4 to 35.1 years. The overall success rate of the total 61 plates was 93.4%. No significant differences were observed among the respective success rates analyzed in accordance with gender, age, side of placement, and length of the screws. The thickness of the bony walls that supported the screws was significantly greater in the success group (mean 1.6 +/- SD, 0.2 vs 1.0 +/- 0.1 mm, P < .001).
Conclusion: Bone thickness is a critical factor in supporting the self-drilling screws and locking plate. Skeletal anchorage combining the plate and 2 screws promises a higher success rate with a thicker bone than with the threshold value of thickness that exists within the 1.1 to 1 4 mm range in the maxillary walls. 2010 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 68:1783-1787, 2010

DOI： 10.1016/j.joms.2009.09.020

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多発性骨髄腫に対するビスフォスフォネート投与に関連したと考えられる上顎骨壊死の1例 International journal

酒井陽, 片桐渉, 服部宇, 金山健夫, 上田実, 山田陽一, 日比英晴, 伊藤憲治

日本口腔科学会雑誌 Vol. 57 ( 3 ) page： 334 - 334 2008.7

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