椎間板髄核細胞と脱分化脂肪細胞（DFAT）との共培養による 細胞間相互作用の解析
腰痛の主原因である椎間板変性症は髄核細胞 (Nucleus pulposus cell: NP cell) の不可逆的な変化が原因であり，根本的な治療法は確立していない．近年，椎間板変性症に対し，再生医学的アプローチを用いた研究が行われてきている．成熟脂肪細胞を天井培養することにより得られる脱分化脂肪細胞 (dedifferentiated fat cell:DFAT) は，間葉系幹細胞に類似した多能性細胞である．本研究は，椎間板変性症に対する DFAT を用いた細胞治療の可能性を明らかにするため，NP cell と DFAT を共培養し，細胞間相互作用による各細胞の増殖活性や形質変化を検討し...
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| Published in | 日大医学雑誌 Vol. 78; no. 5; pp. 285 - 293 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
日本大学医学会
01.10.2019
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0029-0424 1884-0779 |
| DOI | 10.4264/numa.78.5_285 |
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| Abstract | 腰痛の主原因である椎間板変性症は髄核細胞 (Nucleus pulposus cell: NP cell) の不可逆的な変化が原因であり，根本的な治療法は確立していない．近年，椎間板変性症に対し，再生医学的アプローチを用いた研究が行われてきている．成熟脂肪細胞を天井培養することにより得られる脱分化脂肪細胞 (dedifferentiated fat cell:DFAT) は，間葉系幹細胞に類似した多能性細胞である．本研究は，椎間板変性症に対する DFAT を用いた細胞治療の可能性を明らかにするため，NP cell と DFAT を共培養し，細胞間相互作用による各細胞の増殖活性や形質変化を検討した．その結果，NP cell と DFAT を共培養すると，NP cell は細胞増殖能が高まり，DFAT は軟骨分化マーカー遺伝子の発現が増加し，髄核細胞様細胞へと分化することが明らかになった．DFAT は高齢者でも容易に安全かつ簡便な方法で大量調製が可能であるため，椎間板再生医療用の治療用細胞として有用である可能性が示唆された． |
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| AbstractList | 腰痛の主原因である椎間板変性症は髄核細胞 (Nucleus pulposus cell: NP cell) の不可逆的な変化が原因であり，根本的な治療法は確立していない．近年，椎間板変性症に対し，再生医学的アプローチを用いた研究が行われてきている．成熟脂肪細胞を天井培養することにより得られる脱分化脂肪細胞 (dedifferentiated fat cell:DFAT) は，間葉系幹細胞に類似した多能性細胞である．本研究は，椎間板変性症に対する DFAT を用いた細胞治療の可能性を明らかにするため，NP cell と DFAT を共培養し，細胞間相互作用による各細胞の増殖活性や形質変化を検討した．その結果，NP cell と DFAT を共培養すると，NP cell は細胞増殖能が高まり，DFAT は軟骨分化マーカー遺伝子の発現が増加し，髄核細胞様細胞へと分化することが明らかになった．DFAT は高齢者でも容易に安全かつ簡便な方法で大量調製が可能であるため，椎間板再生医療用の治療用細胞として有用である可能性が示唆された． |
| Author | 風間, 智彦 佐久間, 俊行 松本, 太郎 徳橋, 泰明 |
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| References | Strassburg S, Richardson SM, Freemont AJ, et al. Co-cultureinduces mesenchymal stem cell differentiation and modulationof the degenerate human nucleus pulposus cell phenotype.Regen Med 2010; 5: 701–711. Jumabay M, Matsumoto T, Yokoyama S, et al. Dedifferentiated fat cells convert to cardiomyocyte phenotype and repairinfarcted cardiac tissue in rats. J Mol Cell Cardiol 2009; 47:565–575. Nagae M, Ikeda T, Mikami Y, et al. Intervertebral disc regeneration using platelet-rich plasma and biodegradable gelatinhydrogel microspheres. Tissue Eng 2007; 13: 147–158. Pratsinis H, Kletsas D. PDGF, bFGF and IGF-I stimulate theproliferation of intervertebral disc cells in vitro via the activation of the ERK and Akt signaling pathways. Eur Spine J2007; 16: 1858–1866. Sakai D, Mochida J, Yamamoto Y, et al. Transplantation ofmesenchymal stem cells embedded in Atelocollagen gel to theintervertebral disc: a potential therapeutic model for disc degeneration. Biomaterials 2003; 24: 3531–3541. Ariga K, Miyamoto S, Nakase T, et al. The relationship between apoptosis of endplate chondrocytes and aging anddegeneration of the intervertebral disc. Spine 2001; 26: 2414–2420. Shimizu M, Matsumoto T, Kikuta S, et al. Transplantation ofdedifferentiated fat cell-derived micromass pellets contributedto cartilage repair in the rat osteochondral defect model. J Orthop Sci 2018; 23: 688–696. 厚生労働省統計データベース：平成 22 年度国民生活基礎調査 2010；http://wwwdbtk.mhlwgo.jp/toukei/index.html Yamamoto Y, Mochida J, Sakai D, et al. Upregulation of theviability of nucleus pulposus cells by bone marrow-derivedstromal cells: significance of direct cell-to-cell contact in coculture system. Spine 2004; 29: 1508–1514. Matsumoto T, Kano K, Kondo D, et al. Mature adipocytederived dedifferentiated fat cells exhibit multilineage potential. J Cell Physiol 2008; 215: 210–222. Nishimura K, Mochida J. Percutaneous reinsertion of thenucleus pulposus. An experimental study. Spine 1998; 23:1531–1538; discussion 1539. Nishida K, Kang JD, Gilbertson LG, et al. Modulation ofthe biologic activity of the rabbit intervertebral disc by genetherapy: an in vivo study of adenovirus-mediated transfer ofthe human transforming growth factor beta 1 encoding gene.Spine 1999; 24: 2419–2425. Oegema TR, Jr. The role of disc cell heterogeneity in determining disc biochemistry: a speculation. Biochem Soc Trans2002; 30: 839–844. Sakuma T, Matsumoto T, Kano K, et al. Mature, adipocytederived, dedifferentiated fat cells can differentiate into smoothmuscle-like cells and contribute to bladder tissue regeneration.J Urol 2009; 182: 355–365. Nishida K, Doita M, Takada T, et al. Sustained transgeneexpression in intervertebral disc cells in vivo mediated by microbubble-enhanced ultrasound gene therapy. Spine 2006; 31:1415–1419. Urban JP, Smith S, Fairbank JC. Nutrition of the intervertebraldisc. Spine 2004; 29: 2700–2709. Nishida K, Kang JD, Suh JK, et al. Adenovirus-mediatedgene transfer to nucleus pulposus cells. Implications for thetreatment of intervertebral disc degeneration. Spine 1998; 23:2437–2442; discussion 2443. Kikuta S, Tanaka N, Kazama T, et al. Osteogenic effects of dedifferentiated fat cell transplantation in rabbit models of bonedefect and ovariectomy-induced osteoporosis. Tissue Eng PartA 2013; 19: 1792–1802. |
| References_xml | – reference: Nagae M, Ikeda T, Mikami Y, et al. Intervertebral disc regeneration using platelet-rich plasma and biodegradable gelatinhydrogel microspheres. Tissue Eng 2007; 13: 147–158. – reference: 厚生労働省統計データベース：平成 22 年度国民生活基礎調査 2010；http://wwwdbtk.mhlwgo.jp/toukei/index.html – reference: Urban JP, Smith S, Fairbank JC. Nutrition of the intervertebraldisc. Spine 2004; 29: 2700–2709. – reference: Sakai D, Mochida J, Yamamoto Y, et al. Transplantation ofmesenchymal stem cells embedded in Atelocollagen gel to theintervertebral disc: a potential therapeutic model for disc degeneration. Biomaterials 2003; 24: 3531–3541. – reference: Nishida K, Kang JD, Suh JK, et al. Adenovirus-mediatedgene transfer to nucleus pulposus cells. Implications for thetreatment of intervertebral disc degeneration. Spine 1998; 23:2437–2442; discussion 2443. – reference: Sakuma T, Matsumoto T, Kano K, et al. Mature, adipocytederived, dedifferentiated fat cells can differentiate into smoothmuscle-like cells and contribute to bladder tissue regeneration.J Urol 2009; 182: 355–365. – reference: Nishida K, Kang JD, Gilbertson LG, et al. Modulation ofthe biologic activity of the rabbit intervertebral disc by genetherapy: an in vivo study of adenovirus-mediated transfer ofthe human transforming growth factor beta 1 encoding gene.Spine 1999; 24: 2419–2425. – reference: Oegema TR, Jr. The role of disc cell heterogeneity in determining disc biochemistry: a speculation. Biochem Soc Trans2002; 30: 839–844. – reference: Shimizu M, Matsumoto T, Kikuta S, et al. Transplantation ofdedifferentiated fat cell-derived micromass pellets contributedto cartilage repair in the rat osteochondral defect model. J Orthop Sci 2018; 23: 688–696. – reference: Nishimura K, Mochida J. Percutaneous reinsertion of thenucleus pulposus. An experimental study. Spine 1998; 23:1531–1538; discussion 1539. – reference: Strassburg S, Richardson SM, Freemont AJ, et al. Co-cultureinduces mesenchymal stem cell differentiation and modulationof the degenerate human nucleus pulposus cell phenotype.Regen Med 2010; 5: 701–711. – reference: Nishida K, Doita M, Takada T, et al. Sustained transgeneexpression in intervertebral disc cells in vivo mediated by microbubble-enhanced ultrasound gene therapy. Spine 2006; 31:1415–1419. – reference: Jumabay M, Matsumoto T, Yokoyama S, et al. Dedifferentiated fat cells convert to cardiomyocyte phenotype and repairinfarcted cardiac tissue in rats. J Mol Cell Cardiol 2009; 47:565–575. – reference: Yamamoto Y, Mochida J, Sakai D, et al. Upregulation of theviability of nucleus pulposus cells by bone marrow-derivedstromal cells: significance of direct cell-to-cell contact in coculture system. Spine 2004; 29: 1508–1514. – reference: Pratsinis H, Kletsas D. PDGF, bFGF and IGF-I stimulate theproliferation of intervertebral disc cells in vitro via the activation of the ERK and Akt signaling pathways. Eur Spine J2007; 16: 1858–1866. – reference: Matsumoto T, Kano K, Kondo D, et al. Mature adipocytederived dedifferentiated fat cells exhibit multilineage potential. J Cell Physiol 2008; 215: 210–222. – reference: Ariga K, Miyamoto S, Nakase T, et al. The relationship between apoptosis of endplate chondrocytes and aging anddegeneration of the intervertebral disc. Spine 2001; 26: 2414–2420. – reference: Kikuta S, Tanaka N, Kazama T, et al. Osteogenic effects of dedifferentiated fat cell transplantation in rabbit models of bonedefect and ovariectomy-induced osteoporosis. Tissue Eng PartA 2013; 19: 1792–1802. |
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| Snippet | 腰痛の主原因である椎間板変性症は髄核細胞 (Nucleus pulposus cell: NP cell) の不可逆的な変化が原因であり，根本的な治療法は確立していない．近年，椎間板変性症に... |
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| SubjectTerms | 椎間板再生 椎間板変性 細胞治療 脱分化脂肪細胞 髄核細胞 |
| Title | 椎間板髄核細胞と脱分化脂肪細胞（DFAT）との共培養による 細胞間相互作用の解析 |
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