永石　歓和 (ナガイシ　カンナ)

写真a

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医学部 解剖学第二講座

職名

教授

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https://kaken.nii.ac.jp/d/r/30544118.ja.html

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  • 2014年
    　
    　

    札幌医科大学   医学部   講師

    講師

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  • 札幌医科大学   医学部   准教授  

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研究キーワード 【 表示 ／ 非表示 】

  • 消化管運動

  • 糖尿病

  • ストレス科学

  • 炎症性腸疾患

  • 骨髄ニッチ

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論文 【 表示 ／ 非表示 】

  • Down-regulation of RalGTPase-Activating Protein Promotes Colitis-Associated Cancer via NLRP3 Inflammasome Activation

    Tomoya Iida, Daisuke Hirayama, Naoki Minami, Minoru Matsuura, Kohei Wagatsuma, Kentaro Kawakami, Kanna Nagaishi, Masanori Nojima, Hiroki Ikeuchi, Seiichi Hirota, Ryutaro Shirakawa, Hisanori Horiuchi, Hiroshi Nakase

    Cellular and Molecular Gastroenterology and Hepatology ( Elsevier BV )  9 ( 2 ) 277 - 293  2020年  [査読有り]

    DOI PubMed

  • Mitochondria transfer from mesenchymal stem cells structurally and functionally repairs renal proximal tubular epithelial cells in diabetic nephropathy in vivo.

    Konari N, Nagaishi K, Kikuchi S, Fujimiya M

    Scientific reports   9 ( 1 ) 5184 - 5184  2019年03月  [査読有り]  [国際誌]

    　概要を見る

    The underlying therapeutic mechanism of renal tubular epithelium repair of diabetic nephropathy (DN) by bone marrow-derived mesenchymal stem cells (BM-MSCs) has not been fully elucidated. Recently, mitochondria (Mt) transfer was reported as a novel action of BM-MSCs to rescue injured cells. We investigated Mt transfer from systemically administered BM-MSCs to renal proximal tubular epithelial cells (PTECs) in streptozotocin (STZ)-induced diabetic animals. BM-MSCs also transferred their Mt to impaired PTECs when co-cultured in vitro, which suppressed apoptosis of impaired PTECs. Additionally, BM-MSC-derived isolated Mt enhanced the expression of mitochondrial superoxide dismutase 2 and Bcl-2 expression and inhibited reactive oxygen species (ROS) production in vitro. Isolated Mt also inhibited nuclear translocation of PGC-1α and restored the expression of megalin and SGLT2 under high glucose condition (HG) in PTECs. Moreover, isolated Mt directly injected under the renal capsule of STZ rats improved the cellular morphology of STZ-PTECs, and the structure of the tubular basement membrane and brush border in vivo. This study is the first to show Mt transfer from systemically administered BM-MSCs to damaged PTECs in vivo, and the first to investigate mechanisms underlying the potential therapeutic effects of Mt transfer from BM-MSCs in DN.

    DOI PubMed

  • Umbilical cord extracts improve osteoporotic abnormalities of bone marrow-derived mesenchymal stem cells and promote their therapeutic effects on ovariectomised rats

    Akira Saito, Kanna Nagaishi, Kousuke Iba, Yuka Mizue, Takako Chikenji, Miho Otani, Masako Nakano, Kazusa Oyama, Toshihiko Yamashita, Mineko Fujimiya

    Scientific Reports ( Nature Publishing Group )  8 ( 1 ) 1161  2018年12月  [査読有り]

    　概要を見る

    Bone marrow-derived mesenchymal stem cells (BM-MSCs) are the most valuable source of autologous cells for transplantation and tissue regeneration to treat osteoporosis. Although BM-MSCs are the primary cells responsible for maintaining bone metabolism and homeostasis, their regenerative ability may be attenuated in postmenopausal osteoporosis patients. Therefore, we first examined potential abnormalities of BM-MSCs in an oestrogen-deficient rat model constructed by ovariectomy (OVX-MSCs). Cell proliferation, mobilisation, and regulation of osteoclasts were downregulated in OVX-MSCs. Moreover, therapeutic effects of OVX-MSCs were decreased in OVX rats. Accordingly, we developed a new activator for BM-MSCs using human umbilical cord extracts, Wharton's jelly extract supernatant (WJS), which improved cell proliferation, mobilisation and suppressive effects on activated osteoclasts in OVX-MSCs. Bone volume, RANK and TRACP expression of osteoclasts, as well as proinflammatory cytokine expression in bone tissues, were ameliorated by OVX-MSCs activated with WJS (OVX-MSCs-WJ) in OVX rats. Fusion and bone resorption activity of osteoclasts were suppressed in macrophage-induced and primary mouse bone marrow cell-induced osteoclasts via suppression of osteoclast-specific genes, such as Nfatc1, Clcn7, Atp6i and Dc-stamp, by co-culture with OVX-MSCs-WJ in vitro. In this study, we developed a new activator, WJS, which improved the functional abnormalities and therapeutic effects of BM-MSCs on postmenopausal osteoporosis.

    DOI PubMed

  • Activated forms of astrocytes with higher GLT-1 expression are associated with cognitive normal subjects with Alzheimer pathology in human brain.

    Eiji Kobayashi, Masako Nakano, Kenta Kubota, Nobuaki Himuro, Shougo Mizoguchi, Takako Chikenji, Miho Otani, Yuka Mizue, Kanna Nagaishi, Mineko Fujimiya

    Scientific reports   8 ( 1 ) 1712 - 1712  2018年01月  [査読有り]  [国際誌]

    　概要を見る

    Although the cognitive impairment in Alzheimer's disease (AD) is believed to be caused by amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs), several postmortem studies have reported cognitive normal subjects with AD brain pathology. As the mechanism underlying these discrepancies has not been clarified, we focused the neuroprotective role of astrocytes. After examining 47 donated brains, we classified brains into 3 groups, no AD pathology with no dementia (N-N), AD pathology with no dementia (AD-N), and AD pathology with dementia (AD-D), which represented 41%, 21%, and 38% of brains, respectively. No differences were found in the accumulation of Aβ plaques or NFTs in the entorhinal cortex (EC) between AD-N and AD-D. Number of neurons and synaptic density were increased in AD-N compared to those in AD-D. The astrocytes in AD-N possessed longer or thicker processes, while those in AD-D possessed shorter or thinner processes in layer I/II of the EC. Astrocytes in all layers of the EC in AD-N showed enhanced GLT-1 expression in comparison to those in AD-D. Therefore these activated forms of astrocytes with increased GLT-1 expression may exert beneficial roles in preserving cognitive function, even in the presence of Aβ and NFTs.

    DOI PubMed

  • An enriched environment prevents diabetes-induced cognitive impairment in rats by enhancing exosomal miR-146a secretion from endogenous bone marrow-derived mesenchymal stem cells.

    Kenta Kubota, Masako Nakano, Eiji Kobayashi, Yuka Mizue, Takako Chikenji, Miho Otani, Kanna Nagaishi, Mineko Fujimiya

    PloS one   13 ( 9 ) e0204252  2018年  [査読有り]  [国際誌]

    　概要を見る

    Increasing evidence suggests that an enriched environment (EE) ameliorates cognitive impairment by promoting repair of brain damage. However, the mechanisms by which this occurs have not been determined. To address this issue, we investigated whether an EE enhanced the capability of endogenous bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) to prevent hippocampal damage due to diabetes by focusing on miRNA carried in BM-MSC-derived exosomes. In diabetic streptozotocin (STZ) rats housed in an EE (STZ/EE), cognitive impairment was significantly reduced, and both neuronal and astroglial damage in the hippocampus was alleviated compared with STZ rats housed in conventional cages (STZ/CC). BM-MSCs isolated from STZ/CC rats had functional and morphological abnormalities that were not detected in STZ/EE BM-MSCs. The miR-146a levels in exosomes in conditioned medium of cultured BM-MSCs and serum from STZ/CC rats were decreased compared with non-diabetic rats, and the level was restored in STZ/EE rats. Thus, the data suggest that increased levels of miR-146a in sera were derived from endogenous BM-MSCs in STZ/EE rats. To examine the possibility that increased miR-146a in serum may exert anti-inflammatory effects on astrocytes in diabetic rats, astrocytes transfected with miR-146a were stimulated with advanced glycation end products (AGEs) to mimic diabetic conditions. The expression of IRAK1, NF-κB, and tumor necrosis factor-α was significantly higher in AGE-stimulated astrocytes, and these factors were decreased in miR-146a-transfected astrocytes. These results suggested that EEs stimulate up-regulation of exosomal miR-146a secretion by endogenous BM-MSCs, which exerts anti-inflammatory effects on damaged astrocytes and prevents diabetes-induced cognitive impairment.

    DOI PubMed

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Misc 【 表示 ／ 非表示 】

  • 閉経後骨粗鬆症モデルラットに対する賦活化骨髄間葉系幹細胞の治療効果

    齋藤憲, 齋藤憲, 永石歓和, 射場浩介, 山下敏彦, 藤宮峯子

    北海道整形災害外科学会雑誌   61 ( 1 ) 10‐18  2019年08月

    J-GLOBAL

  • 学術奨励賞・受賞記念論文 閉経後骨粗鬆症モデルラットに対する賦活化骨髄間葉系幹細胞の治療効果

    齊藤 憲, 永石 歓和, 射場 浩介, 山下 敏彦, 藤宮 峯子

    北海道整形災害外科学会雑誌 : 北海道整形災害外科学会機関誌 ( 北海道整形災害外科学会 )  61 ( 1 ) 10 - 18  2019年08月

    CiNii

  • 閉経後骨粗鬆症モデルラットに対する賦活化骨髄間葉系幹細胞の治療効果

    齋藤 憲, 永石 歓和, 射場 浩介, 山下 敏彦, 藤宮 峯子

    北海道整形災害外科学会雑誌 ( 北海道整形災害外科学会 )  61 ( 1 ) 10 - 18  2019年08月

    　概要を見る

    閉経後骨粗鬆症は、骨代謝のバランスのうち主に骨吸収が亢進することにより骨量が減少する。骨髄間葉系幹細胞(BM-MSCs)は、骨芽細胞前駆細胞であると共に、破骨細胞の分化・成熟や活性化を制御することで、骨粗鬆症に対する細胞治療において、その病態を改善する効果が期待される。しかし、骨粗鬆症患者由来のBM-MSCsは、様々な細胞機能異常により自家細胞移植に適さない可能性がある。実際、閉経後骨粗鬆症モデルラット由来(OVXラット)のBM-MSCs(OVX-MSCs)は、正常ラットのBM-MSCsに比較して破骨細胞制御能が低下しており、OVXラットに対する治療効果が低下していた。そこで我々は、ヒト臍帯組織抽出物を用いた細胞賦活剤Wharton's jelly extract supernatant(WJS)を独自に開発した。WJSを添加して培養することで、OVX-MSCsの各種機能異常およびOVXラットに対する治療効果が改善した。本賦活剤は、骨粗鬆症患者だけでなく自己BM-MSCsが異常化する他の慢性疾患についても、自家移植による細胞治療の道を拓く可能性がある。(著者抄録)

  • 卵巣摘出閉経後骨粗鬆症モデルラットに対する賦活化骨髄間葉系幹細胞治療の有効性と機序解析

    永石歓和, 藤宮峯子, 齋藤憲, 射場浩介, 山下敏彦

    北海道外科雑誌   64 ( 1 ) 100  2019年06月

    J-GLOBAL

  • 卵巣摘出閉経後骨粗鬆症モデルラットに対する賦活化骨髄間葉系幹細胞治療の有効性と機序解析

    永石 歓和, 藤宮 峯子, 齋藤 憲, 射場 浩介, 山下 敏彦

    北海道外科雑誌 ( 北海道外科学会 )  64 ( 1 ) 100 - 100  2019年06月

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