椎間板針穿刺による椎間板変性ラットに対する脱分化脂肪細胞静脈内投与の治療効果
Intervertebral disc degeneration, a major cause of chronic low back pain, is caused by irreversible changes inthe nucleus pulposus cells that make up part of the disc. In recent years, regenerative medicine for intervertebraldisc degeneration through the administration of mesenchymal stem cells (MSC...
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| Published in | 日大医学雑誌 Vol. 81; no. 5; pp. 273 - 281 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
日本大学医学会
01.10.2022
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0029-0424 1884-0779 |
| DOI | 10.4264/numa.81.5_273 |
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| Abstract | Intervertebral disc degeneration, a major cause of chronic low back pain, is caused by irreversible changes inthe nucleus pulposus cells that make up part of the disc. In recent years, regenerative medicine for intervertebraldisc degeneration through the administration of mesenchymal stem cells (MSCs) and cytokines has been performed. Dedifferentiated fat (DFAT) cells are MSC-like multipotent cells that can be prepared by ceiling cultureof mature adipocytes. In this study, we investigated the effect of intravenous injection of DFAT cells in a ratintervertebral disc degeneration model induced by caudal needle puncture. Radiographic analysis revealed thatintravenous administration of DFAT cells significantly suppressed the narrowing of the intervertebral disc gap.Histological examination revealed that intravenous administration of DFAT cells increased the number of microvessels surrounding the cartilage endplate and intervertebral disc cartilage matrix. Since DFAT cells can becollected and prepared in a minimally invasive procedure even in elderly individuals, DFAT may be an attractivecell source for treating intervertebral disc degeneration. |
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| AbstractList | Intervertebral disc degeneration, a major cause of chronic low back pain, is caused by irreversible changes inthe nucleus pulposus cells that make up part of the disc. In recent years, regenerative medicine for intervertebraldisc degeneration through the administration of mesenchymal stem cells (MSCs) and cytokines has been performed. Dedifferentiated fat (DFAT) cells are MSC-like multipotent cells that can be prepared by ceiling cultureof mature adipocytes. In this study, we investigated the effect of intravenous injection of DFAT cells in a ratintervertebral disc degeneration model induced by caudal needle puncture. Radiographic analysis revealed thatintravenous administration of DFAT cells significantly suppressed the narrowing of the intervertebral disc gap.Histological examination revealed that intravenous administration of DFAT cells increased the number of microvessels surrounding the cartilage endplate and intervertebral disc cartilage matrix. Since DFAT cells can becollected and prepared in a minimally invasive procedure even in elderly individuals, DFAT may be an attractivecell source for treating intervertebral disc degeneration. |
| Author | 上井, 浩 中西, 一義 宮方, 啓行 風間, 智彦 小山, 公行 松本, 太郎 德橋, 泰明 |
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| References | 2) Nishida K, Kang JD, Gilbertson LG, et al. Modulation of the biologic activity of the rabbit intervertebral disc by gene therapy: an in vivo study of adenovirusmediated transfer of the human transforming growth factor beta 1 encoding gene. Spine 1999; 24: 2419–2425. 18) Matsumine H, Takeuchi Y, Sasaki R, et al. Adipocytederived and dedifferentiated fat cells promoting facial nerve regenera tion in a rat model. Plast Reconstr Surg 2014; 134: 686–697. 20) Wang Z, Perez-Terzic CM, Smith J, et al. Efficacy of interver tebral disc regeneration with stem cells – a systematic review and metaanalysis of animal controlled trials. Gene 2015; 564: 1–8. 4) Nagae M, Ikeda T, Mikami Y, et al. Intervertebral disc regen eration using plateletrich plasma and biodegradable gelatin hydrogel microspheres. Tissue Eng 2007; 13: 147–158. 5) Nishimura K, Mochida J. Percutaneous reinsertion of the nu cleus pulposus. An experimental study. Spine 1998; 23: 1531– 1538; discussion 1539. 14) Maruyama T, Fukuda N, Matsumoto T, et al. Systematic im plantation of dedifferentiated fat cells ameliorated monoclonal antibody 1223induced glomerulonephritis by immunosup pression with increases in TNFstimulated gene 6. Stem Cell Res Ther 2015; 6: 80. 9) Uchio Y, Ochi M, Matsusaki M, et al. Human chondrocyte proliferation and matrix synthesis cultured in Atelocollagen gel. J Biomed Mater Res 2000; 50: 138–143. 1) Nishida K, Kang JD, Suh JK, et al. Adenovirusmediated gene transfer to nucleus pulposus cells. Implications for the treatment of intervertebral disc degeneration. Spine 1998; 23: 2437–2442; discussion 2443. 8) Crevensten G, Walsh AJ, Ananthakrishnan D, et al. Interverte bral disc cell therapy for regeneration: mesenchymal stem cell implantation in rat intervertebral discs. Ann Biomed Eng 2004; 32: 430–434. 3) Nishida K, Doita M, Takada T, et al. Sustained transgene expression in intervertebral disc cells in vivo mediated by microbubbleenhanced ultrasound gene therapy. Spine 2006; 31: 1415–1419. 7) Sakai D, Mochida J, Iwashina T, et al. Differentiation of mes enchymal stem cells transplanted to a rabbit degenerative disc model: potential and limitations for stem cell therapy in disc regeneration. Spine 2005; 30: 2379–2387. 6) Yamamoto Y, Mochida J, Sakai D, et al. Upregulation of the viability of nucleus pulposus cells by bone marrowderived stromal cells: significance of direct cell-to-cell contact in coculture system. Spine 2004; 29: 1508–1514. 16) Jumabay M, Matsumoto T, Yokoyama S, et al. Dedifferenti ated fat cells convert to cardiomyocyte phenotype and repair infarcted cardiac tissue in rats. J Mol Cell Cardiol 2009; 47: 565–575. 10) Matsumoto T, Kano K, Kondo D, et al. Mature adipocyte derived dedifferentiated fat cells exhibit multilineage potential. J Cell Physiol 2008; 215: 210–222. 12) Issy AC, Castania V, Castania M, et al. Experimental model of intervertebral disc degeneration by needle puncture in Wistar rats. Braz J Med Biol Res 2013; 46: 235–244. 15) Risbud MV, Shapiro IM. Role of cytokines in intervertebral disc degeneration: pain and disc content. Nat Rev Rheumatol 2014; 10: 44–56. 13) Lee RH, Pulin AA, Seo MJ, et al. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell 2009; 5: 54–63. 19) Watanabe H, Goto S, Kato R, et al. The neovascularization effect of dedifferentiated fat cells. Sci Rep 2020; 10: 9211. 11) Rodemann HP, Bayreuther K. Abnormal collagen metabolism in cultured skin fibroblasts from patients with Duchenne mus cular dystrophy. Proc Natl Acad Sci U S A 1984; 81: 5130– 5134. 17) Soejima K, Kashimura T, Asami T, et al. Effects of mature adi pocyte-derived dedifferentiated fat (DFAT) cells on generation and vascularisation of dermis-like tissue after artificial dermis grafting. J Plast Surg Hand Surg 2015; 49: 25–31. |
| References_xml | – reference: 13) Lee RH, Pulin AA, Seo MJ, et al. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell 2009; 5: 54–63. – reference: 3) Nishida K, Doita M, Takada T, et al. Sustained transgene expression in intervertebral disc cells in vivo mediated by microbubbleenhanced ultrasound gene therapy. Spine 2006; 31: 1415–1419. – reference: 1) Nishida K, Kang JD, Suh JK, et al. Adenovirusmediated gene transfer to nucleus pulposus cells. Implications for the treatment of intervertebral disc degeneration. Spine 1998; 23: 2437–2442; discussion 2443. – reference: 18) Matsumine H, Takeuchi Y, Sasaki R, et al. Adipocytederived and dedifferentiated fat cells promoting facial nerve regenera tion in a rat model. Plast Reconstr Surg 2014; 134: 686–697. – reference: 14) Maruyama T, Fukuda N, Matsumoto T, et al. Systematic im plantation of dedifferentiated fat cells ameliorated monoclonal antibody 1223induced glomerulonephritis by immunosup pression with increases in TNFstimulated gene 6. Stem Cell Res Ther 2015; 6: 80. – reference: 9) Uchio Y, Ochi M, Matsusaki M, et al. Human chondrocyte proliferation and matrix synthesis cultured in Atelocollagen gel. J Biomed Mater Res 2000; 50: 138–143. – reference: 4) Nagae M, Ikeda T, Mikami Y, et al. Intervertebral disc regen eration using plateletrich plasma and biodegradable gelatin hydrogel microspheres. Tissue Eng 2007; 13: 147–158. – reference: 19) Watanabe H, Goto S, Kato R, et al. The neovascularization effect of dedifferentiated fat cells. Sci Rep 2020; 10: 9211. – reference: 15) Risbud MV, Shapiro IM. Role of cytokines in intervertebral disc degeneration: pain and disc content. Nat Rev Rheumatol 2014; 10: 44–56. – reference: 20) Wang Z, Perez-Terzic CM, Smith J, et al. Efficacy of interver tebral disc regeneration with stem cells – a systematic review and metaanalysis of animal controlled trials. Gene 2015; 564: 1–8. – reference: 17) Soejima K, Kashimura T, Asami T, et al. Effects of mature adi pocyte-derived dedifferentiated fat (DFAT) cells on generation and vascularisation of dermis-like tissue after artificial dermis grafting. J Plast Surg Hand Surg 2015; 49: 25–31. – reference: 8) Crevensten G, Walsh AJ, Ananthakrishnan D, et al. Interverte bral disc cell therapy for regeneration: mesenchymal stem cell implantation in rat intervertebral discs. Ann Biomed Eng 2004; 32: 430–434. – reference: 12) Issy AC, Castania V, Castania M, et al. Experimental model of intervertebral disc degeneration by needle puncture in Wistar rats. Braz J Med Biol Res 2013; 46: 235–244. – reference: 10) Matsumoto T, Kano K, Kondo D, et al. Mature adipocyte derived dedifferentiated fat cells exhibit multilineage potential. J Cell Physiol 2008; 215: 210–222. – reference: 11) Rodemann HP, Bayreuther K. Abnormal collagen metabolism in cultured skin fibroblasts from patients with Duchenne mus cular dystrophy. Proc Natl Acad Sci U S A 1984; 81: 5130– 5134. – reference: 5) Nishimura K, Mochida J. Percutaneous reinsertion of the nu cleus pulposus. An experimental study. Spine 1998; 23: 1531– 1538; discussion 1539. – reference: 7) Sakai D, Mochida J, Iwashina T, et al. Differentiation of mes enchymal stem cells transplanted to a rabbit degenerative disc model: potential and limitations for stem cell therapy in disc regeneration. Spine 2005; 30: 2379–2387. – reference: 16) Jumabay M, Matsumoto T, Yokoyama S, et al. Dedifferenti ated fat cells convert to cardiomyocyte phenotype and repair infarcted cardiac tissue in rats. J Mol Cell Cardiol 2009; 47: 565–575. – reference: 2) Nishida K, Kang JD, Gilbertson LG, et al. Modulation of the biologic activity of the rabbit intervertebral disc by gene therapy: an in vivo study of adenovirusmediated transfer of the human transforming growth factor beta 1 encoding gene. Spine 1999; 24: 2419–2425. – reference: 6) Yamamoto Y, Mochida J, Sakai D, et al. Upregulation of the viability of nucleus pulposus cells by bone marrowderived stromal cells: significance of direct cell-to-cell contact in coculture system. Spine 2004; 29: 1508–1514. |
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| SubjectTerms | 再生医療 椎間板変性症 細胞治療 脱分化脂肪細胞 |
| Title | 椎間板針穿刺による椎間板変性ラットに対する脱分化脂肪細胞静脈内投与の治療効果 |
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