間葉系幹細胞による関節リウマチの骨軟骨再生へのアプローチ
関節リウマチ（RA）は関節炎と関節の構造的障害を特徴とする疾患で，進行すると身体機能障害を引き起こし，就労率の低下や介護といった社会資源の損失をもたらす．元来RAは進行性の疾患と考えられていたが，近年の治療の進歩により関節破壊の完全な進展抑制が現実的となった．しかし，罹病期間が長く新治療の恩恵を受けられなかった，または新治療によっても疾患活動性が制御できないなどの理由で進行した関節破壊を呈する患者は稀でなく，破壊関節を再生しうる治療法の開発が待たれている．我々は，骨・軟骨に分化可能で抗炎症作用を持つ間葉系幹細胞（MSC）による治療をRAの新規治療法として位置づけ，これまでにMSCが破骨細胞分化...
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| Published in | JOURNAL OF UOEH Vol. 36; no. 2; pp. 141 - 146 |
|---|---|
| Main Authors | , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
学校法人 産業医科大学
01.06.2014
産業医科大学 |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0387-821X 2187-2864 |
| DOI | 10.7888/juoeh.36.141 |
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| Abstract | 関節リウマチ（RA）は関節炎と関節の構造的障害を特徴とする疾患で，進行すると身体機能障害を引き起こし，就労率の低下や介護といった社会資源の損失をもたらす．元来RAは進行性の疾患と考えられていたが，近年の治療の進歩により関節破壊の完全な進展抑制が現実的となった．しかし，罹病期間が長く新治療の恩恵を受けられなかった，または新治療によっても疾患活動性が制御できないなどの理由で進行した関節破壊を呈する患者は稀でなく，破壊関節を再生しうる治療法の開発が待たれている．我々は，骨・軟骨に分化可能で抗炎症作用を持つ間葉系幹細胞（MSC）による治療をRAの新規治療法として位置づけ，これまでにMSCが破骨細胞分化抑制作用を持つこと，炎症がMSCの骨芽細胞分化を促進し，軟骨細胞分化を抑制することを報告した．さらに現在，足場によるMSC移植システムを構築中であり，RA患者への臨床応用は着実に近づきつつあると考えられる． |
|---|---|
| AbstractList | 関節リウマチ（RA）は関節炎と関節の構造的障害を特徴とする疾患で，進行すると身体機能障害を引き起こし，就労率の低下や介護といった社会資源の損失をもたらす．元来RAは進行性の疾患と考えられていたが，近年の治療の進歩により関節破壊の完全な進展抑制が現実的となった．しかし，罹病期間が長く新治療の恩恵を受けられなかった，または新治療によっても疾患活動性が制御できないなどの理由で進行した関節破壊を呈する患者は稀でなく，破壊関節を再生しうる治療法の開発が待たれている．我々は，骨・軟骨に分化可能で抗炎症作用を持つ間葉系幹細胞（MSC）による治療をRAの新規治療法として位置づけ，これまでにMSCが破骨細胞分化抑制作用を持つこと，炎症がMSCの骨芽細胞分化を促進し，軟骨細胞分化を抑制することを報告した．さらに現在，足場によるMSC移植システムを構築中であり，RA患者への臨床応用は着実に近づきつつあると考えられる． 「要旨」:関節リウマチ(RA)は関節炎と関節の構造的障害を特徴とする疾患で, 進行すると身体機能障害を引き起こし, 就労率の低下や介護といった社会資源の損失をもたらす. 元来RAは進行性の疾患と考えられていたが, 近年の治療の進歩により関節破壊の完全な進展抑制が現実的となった. しかし, 罹病期間が長く新治療の恩恵を受けられなかった, または新治療によっても疾患活動性が制御できないなどの理由で進行した関節破壊を呈する患者は稀でなく, 破壊関節を再生しうる治療法の開発が待たれている. 我々は, 骨・軟骨に分化可能で抗炎症作用を持つ間葉系幹細胞(MSC)による治療をRAの新規治療法として位置づけ, これまでにMSCが破骨細胞分化抑制作用を持つこと, 炎症がMSCの骨芽細胞分化を促進し, 軟骨細胞分化を抑制することを報告した. さらに現在, 足場によるMSC移植システムを構築中であり, RA患者への臨床応用は着実に近づきつつあると考えられる. |
| Author | 田中, 良哉 園本, 格士朗 山岡, 邦宏 |
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| References | 6. エーザイ株式会社 & アッヴィ合同会社 （2012）：ヒュミラ適正使用情報 7: 4 8. Campagnoli C, Roberts IA, Kumar S, Bennett PR, Bellantuono I & Fisk NM (2001): Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood 98: 2396-2402 24. Baron R & Kneissel M (2013): WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med 19: 179-192 25. Sonomoto K, Yamaoka K, Oshita K, Fukuyo S, Zhang X, Nakano K, Okada Y & Tanaka Y (2012): Interleukin-1beta induces differentiation of human mesenchymal stem cells into osteoblasts via the Wnt-5a/receptor tyrosine kinase-like orphan receptor 2 pathway. Arthritis Rheum 64: 3355-3363 11. Zuk PA, Zhu M, Ashjian P, De Ugarte DA , Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P & Hedrick MH (2002): Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13: 4279-4295 29. Gao J, Dennis JE, Muzic RF, Lundberg M & Caplan AI (2001): The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells Tissues Organs 169: 12-20 7. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S & Marshak DR (1999): Multilineage potential of adult human mesenchymal stem cells. Science 284: 143-147 31. Perez-Cano R, Vranckx JJ, Lasso JM, Calabrese C, Merck B, Milstein AM, Sassoon E, Delay E & Weiler-Mithoff EM (2012): Prospective trial of adipose-derived regenerative cell (ADRC)-enriched fat grafting for partial mastectomy defects: the RESTORE-2 trial. Eur J Surg Oncol 38: 382-389 32. Fukuyo S, Yamaoka K, Sonomoto K, Oshita K, Okada Y, Saito K, Yoshida Y, Kanazawa T, Minami Y & Tanaka Y (2014): IL-6-accelerated calcification by induction of ROR2 in human adipose tissue-derived mesenchymal stem cells is STAT3-dependent. Rheumatology (Oxford) (in press) 1. Lipsky PE (2008): Rheumatoid arthritis. In: Harrison’s principles of internal medicine. 17th. (Harrison TR ed). McGraw-Hill, New York pp 2083-2092 27. Chabaud M, Durand JM, Buchs N, Fossiez F, Page G, Frappart L & Miossec P (1999): Human interleukin-17: A T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum 42: 963-970 9. In’t Anker PS, Scherjon SA, Kleijburg-van der Keur C, Noort WA, Claas FH, Willemze R, Fibbe WE & Kanhai HH (2003): Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood 102: 1548-1549 10. Nakahara H, Dennis JE, Bruder SP, Haynesworth SE, Lennon DP & Caplan AI (1991): In vitro differentiation of bone and hypertrophic cartilage from periosteal-derived cells. Exp Cell Res 195: 492-503 19. Walsh NC, Reinwald S, Manning CA, Condon KW, Iwata K, Burr DB & Gravallese EM (2009): Osteoblast function is compromised at sites of focal bone erosion in inflammatory arthritis. J Bone Miner Res 24: 1572-1585 12. Uccelli A, Moretta L & Pistoia V (2008): Mesenchymal stem cells in health and disease. Nat Rev Immunol 8: 726-736 3. Takeuchi T, Yamanaka H, Inoue E et al (2008): Retrospective clinical study on the notable efficacy and related factors of infliximab therapy in a rheumatoid arthritis management group in Japan: one-year outcome of joint destruction (RECONFIRM-2J). Mod Rheumatol 18: 447-454 22. Habas R, Dawid IB & He X (2003): Coactivation of Rac and Rho by Wnt/Frizzled signaling is required for vertebrate gastrulation. Genes Dev 17: 295-309 15. Takayanagi H (2009): Osteoimmunology and the effects of the immune system on bone. Nat Rev Rheumatol 5: 667-676 2. Tanaka Y, Takeuchi T, Inoue E et al (2008): Retrospective clinical study on the notable efficacy and related factors of infliximab therapy in a rheumatoid arthritis management group in Japan: one-year clinical outcomes (RECONFIRM-2). Mod Rheumatol 18: 146-152 4. Fuchs HA, Kaye JJ, Callahan LF, Nance EP & Pincus T (1989): Evidence of significant radiographic damage in rheumatoid arthritis within the first 2 years of disease. J Rheumatol 16: 585-591 13. Le Blanc K, Frassoni F, Ball L et al (2008): Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 371: 1579-1586 5. Takeuchi T, Tatsuki Y, Nogami Y et al (2008): Postmarketing surveillance of the safety profile of infliximab in 5000 Japanese patients with rheumatoid arthritis. Ann Rheum Dis 67: 189-194 18. Oshita K, Yamaoka K & Tanaka Y (2013): Regulation of osteoclastogenesis by human mesenchymal stem cells leading to application of a novel treatment for rheumatoid arthritis. J UOEH 35: 33-37 20. Moon RT, Bowerman B, Boutros M & Perrimon N (2002): The promise and perils of Wnt signaling through beta-catenin. Science 296: 1644-1646 28. Kondo M, Yamaoka K, Sonomoto K, Fukuyo S, Oshita K, Okada Y & Tanaka Y (2013): IL-17 inhibits chondrogenic differentiation of human mesenchymal stem cells. PLoS One 8: e79463 21. Wang HY & Malbon CC (2003): Wnt signaling, Ca2+, and cyclic GMP: visualizing Frizzled functions. Science 300: 1529-1530 30. Gonzalez MA, Gonzalez-Rey E, Rico L, Buscher D & Delgado M (2009): Treatment of experimental arthritis by inducing immune tolerance with human adipose-derived mesenchymal stem cells. Arthritis Rheum 60: 1006-1019 17. Oshita K, Yamaoka K, Udagawa N et al (2011): Human mesenchymal stem cells inhibit osteoclastogenesis through osteoprotegerin production. Arthritis Rheum 63: 1658-1667 16. Gravallese EM, Manning C, Tsay A, Naito A, Pan C, Amento E & Goldring SR (2000): Synovial tissue in rheumatoid arthritis is a source of osteoclast differentiation factor. Arthritis Rheum 43: 250-258 26. Wehling N, Palmer GD, Pilapil C, Liu F, Wells JW, Muller PE, Evans CH & Porter RM (2009): Interleukin-1β and tumor necrosis factor alpha inhibit chondrogenesis by human mesenchymal stem cells through NF-kB-dependent pathways. Arthritis Rheum 60: 801-812 33. Sonomoto K, Yamaoka K, Zhang X & Tanaka Y (2012): Mesenchymal stem cells: A new treatment tool for rheumatoid arthritis. Inflammation Regenerat 32: 188-192 14. Udagawa N, Takahashi N, Yasuda H et al (2000): Osteoprotegerin produced by osteoblasts is an important regulator in osteoclast development and function. Endocrinology 141: 3478-3484 23. Lories RJ, Corr M & Lane NE (2013): To Wnt or not to Wnt: the bone and joint health dilemma. Nat Rev Rheumatol 9: 328-339 |
| References_xml | – reference: 7. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S & Marshak DR (1999): Multilineage potential of adult human mesenchymal stem cells. Science 284: 143-147 – reference: 10. Nakahara H, Dennis JE, Bruder SP, Haynesworth SE, Lennon DP & Caplan AI (1991): In vitro differentiation of bone and hypertrophic cartilage from periosteal-derived cells. Exp Cell Res 195: 492-503 – reference: 33. Sonomoto K, Yamaoka K, Zhang X & Tanaka Y (2012): Mesenchymal stem cells: A new treatment tool for rheumatoid arthritis. Inflammation Regenerat 32: 188-192 – reference: 8. Campagnoli C, Roberts IA, Kumar S, Bennett PR, Bellantuono I & Fisk NM (2001): Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood 98: 2396-2402 – reference: 18. Oshita K, Yamaoka K & Tanaka Y (2013): Regulation of osteoclastogenesis by human mesenchymal stem cells leading to application of a novel treatment for rheumatoid arthritis. J UOEH 35: 33-37 – reference: 28. Kondo M, Yamaoka K, Sonomoto K, Fukuyo S, Oshita K, Okada Y & Tanaka Y (2013): IL-17 inhibits chondrogenic differentiation of human mesenchymal stem cells. PLoS One 8: e79463 – reference: 30. Gonzalez MA, Gonzalez-Rey E, Rico L, Buscher D & Delgado M (2009): Treatment of experimental arthritis by inducing immune tolerance with human adipose-derived mesenchymal stem cells. Arthritis Rheum 60: 1006-1019 – reference: 14. Udagawa N, Takahashi N, Yasuda H et al (2000): Osteoprotegerin produced by osteoblasts is an important regulator in osteoclast development and function. Endocrinology 141: 3478-3484 – reference: 17. Oshita K, Yamaoka K, Udagawa N et al (2011): Human mesenchymal stem cells inhibit osteoclastogenesis through osteoprotegerin production. Arthritis Rheum 63: 1658-1667 – reference: 22. Habas R, Dawid IB & He X (2003): Coactivation of Rac and Rho by Wnt/Frizzled signaling is required for vertebrate gastrulation. Genes Dev 17: 295-309 – reference: 3. Takeuchi T, Yamanaka H, Inoue E et al (2008): Retrospective clinical study on the notable efficacy and related factors of infliximab therapy in a rheumatoid arthritis management group in Japan: one-year outcome of joint destruction (RECONFIRM-2J). Mod Rheumatol 18: 447-454 – reference: 25. Sonomoto K, Yamaoka K, Oshita K, Fukuyo S, Zhang X, Nakano K, Okada Y & Tanaka Y (2012): Interleukin-1beta induces differentiation of human mesenchymal stem cells into osteoblasts via the Wnt-5a/receptor tyrosine kinase-like orphan receptor 2 pathway. Arthritis Rheum 64: 3355-3363 – reference: 9. In’t Anker PS, Scherjon SA, Kleijburg-van der Keur C, Noort WA, Claas FH, Willemze R, Fibbe WE & Kanhai HH (2003): Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood 102: 1548-1549 – reference: 31. Perez-Cano R, Vranckx JJ, Lasso JM, Calabrese C, Merck B, Milstein AM, Sassoon E, Delay E & Weiler-Mithoff EM (2012): Prospective trial of adipose-derived regenerative cell (ADRC)-enriched fat grafting for partial mastectomy defects: the RESTORE-2 trial. Eur J Surg Oncol 38: 382-389 – reference: 4. Fuchs HA, Kaye JJ, Callahan LF, Nance EP & Pincus T (1989): Evidence of significant radiographic damage in rheumatoid arthritis within the first 2 years of disease. J Rheumatol 16: 585-591 – reference: 21. Wang HY & Malbon CC (2003): Wnt signaling, Ca2+, and cyclic GMP: visualizing Frizzled functions. Science 300: 1529-1530 – reference: 16. Gravallese EM, Manning C, Tsay A, Naito A, Pan C, Amento E & Goldring SR (2000): Synovial tissue in rheumatoid arthritis is a source of osteoclast differentiation factor. Arthritis Rheum 43: 250-258 – reference: 24. Baron R & Kneissel M (2013): WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med 19: 179-192 – reference: 32. Fukuyo S, Yamaoka K, Sonomoto K, Oshita K, Okada Y, Saito K, Yoshida Y, Kanazawa T, Minami Y & Tanaka Y (2014): IL-6-accelerated calcification by induction of ROR2 in human adipose tissue-derived mesenchymal stem cells is STAT3-dependent. Rheumatology (Oxford) (in press) – reference: 12. Uccelli A, Moretta L & Pistoia V (2008): Mesenchymal stem cells in health and disease. Nat Rev Immunol 8: 726-736 – reference: 19. Walsh NC, Reinwald S, Manning CA, Condon KW, Iwata K, Burr DB & Gravallese EM (2009): Osteoblast function is compromised at sites of focal bone erosion in inflammatory arthritis. J Bone Miner Res 24: 1572-1585 – reference: 20. Moon RT, Bowerman B, Boutros M & Perrimon N (2002): The promise and perils of Wnt signaling through beta-catenin. Science 296: 1644-1646 – reference: 29. Gao J, Dennis JE, Muzic RF, Lundberg M & Caplan AI (2001): The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells Tissues Organs 169: 12-20 – reference: 5. Takeuchi T, Tatsuki Y, Nogami Y et al (2008): Postmarketing surveillance of the safety profile of infliximab in 5000 Japanese patients with rheumatoid arthritis. Ann Rheum Dis 67: 189-194 – reference: 26. Wehling N, Palmer GD, Pilapil C, Liu F, Wells JW, Muller PE, Evans CH & Porter RM (2009): Interleukin-1β and tumor necrosis factor alpha inhibit chondrogenesis by human mesenchymal stem cells through NF-kB-dependent pathways. Arthritis Rheum 60: 801-812 – reference: 13. Le Blanc K, Frassoni F, Ball L et al (2008): Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 371: 1579-1586 – reference: 2. Tanaka Y, Takeuchi T, Inoue E et al (2008): Retrospective clinical study on the notable efficacy and related factors of infliximab therapy in a rheumatoid arthritis management group in Japan: one-year clinical outcomes (RECONFIRM-2). Mod Rheumatol 18: 146-152 – reference: 27. Chabaud M, Durand JM, Buchs N, Fossiez F, Page G, Frappart L & Miossec P (1999): Human interleukin-17: A T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum 42: 963-970 – reference: 1. Lipsky PE (2008): Rheumatoid arthritis. In: Harrison’s principles of internal medicine. 17th. (Harrison TR ed). McGraw-Hill, New York pp 2083-2092 – reference: 15. Takayanagi H (2009): Osteoimmunology and the effects of the immune system on bone. Nat Rev Rheumatol 5: 667-676 – reference: 11. Zuk PA, Zhu M, Ashjian P, De Ugarte DA , Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P & Hedrick MH (2002): Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13: 4279-4295 – reference: 23. Lories RJ, Corr M & Lane NE (2013): To Wnt or not to Wnt: the bone and joint health dilemma. Nat Rev Rheumatol 9: 328-339 – reference: 6. エーザイ株式会社 & アッヴィ合同会社 （2012）：ヒュミラ適正使用情報 7: 4 |
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| Snippet | ... 「要旨」:関節リウマチ(RA)は関節炎と関節の構造的障害を特徴とする疾患で, 進行すると身体機能障害を引き起こし, 就労率の低下や介護といった社会資源の損失をもたらす. 元来RAは進行性の疾患と考えられていたが, 近年の治療の進歩により関節破壊の完全な進展抑制が現実的となった. しかし,... |
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| Title | 間葉系幹細胞による関節リウマチの骨軟骨再生へのアプローチ |
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| ispartofPNX | Journal of UOEH, 2014/06/01, Vol.36(2), pp.141-146 |
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