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陳 国平 再生医療を支える バイオマテリアルの研究開発
⏕་⒪ࢆᨭ࠼ࡿ ࣂ࣐࢜ࢸࣜࣝࡢ◊✲㛤Ⓨ 㝞 ᅜᖹ ≀㉁࣭ᮦᩱ◊✲ᶵᵓ ᅜ㝿ࢼࣀ࣮࢟ࢸࢡࢺࢽࢡࢫ◊✲ᣐⅬ Ẽࡸࡅࡀࡢᚑ᮶ࡢ⒪ἲ ᢞ⸆⒪ ேᕤ⮚ჾ ⤌⧊࣭⮚ჾ ᦆኻ 㐺⏝⠊ᅖࡀ 㝈ᐃࡉࢀࡿ 㒊ศⓗᶵ⬟ࡢ௦᭰ ⤒ᖺຎ ⮚ჾ⛣᳜ ࢻࢼ࣮㊊ චᣄ⤯ᛂ ඛ㐍་⒪ࡋ࡚ࡢ⏕་⒪ ᢞ⸆⒪ ேᕤ⮚ჾ ⤌⧊࣭⮚ჾࠊᦆኻ 㐺⏝⠊ᅖࡀ 㝈ᐃࡉࢀࡿ 㒊ศⓗᶵ⬟ ࡢ௦᭰ ⮚ჾ⛣᳜ ࢻࢼ࣮㊊ චᣄ⤯ᛂ ⏕་⒪ ᚑ᮶ࡢ⒪ἲࢃࡗ࡚ࠊᝈ⪅⮬㌟ࡢ⣽⬊ࢆᇵ㣴ࡋࠊᚲせ࡞⤌⧊࣭ ⮚ჾࢆᵓ⠏ࡋ࡚⛣᳜ࡍࡿ⒪ἲ㸦⏕་⒪㸧ࡀᮇᚅࡉࢀ࡚࠸ࡿࠋ 㛵⠇㌾㦵ࡢ⏕ ⣽⬊ᇵ㣴 ⛣᳜ ⏕㌾㦵 ㌾㦵Ḟᦆ 㸦㈇യࡼࡿ㒊ศḞᦆࠊ ኚᙧᛶ㛵⠇࡞㸧 ⏕་⒪ࡢᕷሙつᶍ ேᕤ㛵⠇ ⣙൨ 㦵᥋ྜᮦᩱ ⣙൨ ⬨᳝ᅛᐃ⏝ල ⣙൨ ேᕤ㦵 ⣙൨ ேᕤ┿⓶ ⣙൨ (http://www.yano.co.jp/, http://www.wound-treatment.jp/, http://www.jmdm.co.jp/ ࡞ࢆཧ⪃⦅㞟 ⏕་⒪〇ရࡢᅜෆᕷሙつᶍࡣ㧗㱋⪅ேཱྀࡢቑຍక࠸ࠊ ᖺࡣࡶཬࡪᕧ⏘ᴗᡂ㛗ࡍࡿண ࠋ 㸦㺀ᖺ∧⏕་⒪ࣅࢪࢿࢫࡢ᭱᪂ືྥ㺁ࢩ࣮ࢻ࣭ࣉࣛࣥࢽࣥࢢ♫ࡼࡾ㸧 ⏕་⒪ࡢせ⣲ᢏ⾡ ࡼ࠸⏕యᮦᩱࡀᚲせ ୕せ⣲ ⤌⧊⏕ ⮫ᗋᛂ⏝ 㦵 ⣽⬊ ⣽⬊ᡂ㛗ᅉᏊ ㌾㦵 ⓶ ⏕యᮦᩱ㸦㊊ሙᮦᩱ㸧 ⫢⮚ ᝈ⪅ NIMSࡀ ࡀ㛤Ⓨࡋࡓᶵ⬟ᛶ⏕యᮦᩱ㸦ከᏍ㉁㊊ሙᮦᩱ㸧 Collagen Sponge PLGA-Collagen Hybrid Mesh PLGA-Collagen PLGA A Collagen Hy Hybrid Sponge Biphasic Scaffold Leakproof Scaffold ịᚤ⢏Ꮚࢆ⏝ࡋࡓከᏍ㉁㊊ሙᮦᩱࡢస〇ᢏ⾡ ࣐ࢡࣟỈࡢస〇㻌 ᄇ㟝㻌 ࢥ࣮ࣛࢤࣥ⁐ᾮ㻌 ịᚤ⢏Ꮚࡢ㗪ᆺ㻌 ⣧Ỉ㻌 ịᚤ⢏Ꮚ㻌 ⁐ᾮࡢ㻌 ῧຍ㻌 Ỉᛶ⾲㠃 タᐃࡋࡓ ᗘ࡛㸯 㛫㟼⨨ࡋࠊ⤖ ࣈࣇࢼ࣮₃ᩯ ⤖⇱ ࡁ࡞⾲㠃✵Ꮝ ᯫᶫ Ὑί ₃ᩯ≧ࢥ࣮ࣛࢤࣥࢫ࣏ࣥࢪ㻌 ෆ㒊✵Ꮝ㻌 ࣃࢱ࣮ࣥࡋࡓịᚤ⢏Ꮚࡢ㗪ᆺ ịᚤ⢏Ꮚ࡛స〇ࡋࡓࣃࢱ࣮ࣥከᏍ㉁㊊ሙᮦᩱ ࣐ࢡࣟࣃࢱ࣮ࣥከᏍ㉁㊊ሙᮦᩱࢆ⏝࠸࡚⏕ࡋࡓ➽⫗⤌⧊ F-actin Nuclei F-actin Nuclei Nuclei MHC MHC Nuclei Scale bar = 200 μm ịᚤ⢏Ꮚࢆ⏝ࡋࡓከᏍ㉁㊊ሙᮦᩱస〇ἲࡢ≉㛗 㸯㸬✵Ꮝࡢᙧ≧ࡸᏍᚄࢆ⢭ᐦไᚚ࡛ࡁࡿ 㸰㸬⾲㠃ࡢ㛤ཱྀከᏍ㉁ᵓ㐀ࢆస〇࡛ࡁࡿ 㸱㸬ࢧࢬࡀᥞࡗࡓ✵Ꮝࢆస〇ࡍࡿࡇࡀྍ⬟ 㸲㸬✵ᏍⰋ࠸㐃㏻ᛶࡀ࠶ࡿ 㸳㸬ịᚤ⢏Ꮚࢆ⏝ࡍࡿࡇ࡛ࠊከᏍ㉁ᵓ㐀ᙧᡂࢆὙί㝖ཤࡍࡿ ᚲせࡀ࡞ࡃࠊ⤖⇱ࡢࡳ࡛㝖ཤࡉࢀࡿ 㸴㸬࣐ࢡࣟࣃࢱ࣮ࣥࡋࡓከᏍ㉁ᵓ㐀ࡢฟࡀྍ⬟ 㸵㸬⣽⬊ᡂ㛗ᅉᏊ࡞ࡢ⏕⌮άᛶ≀㉁ࡢ࣐ࢡࣟࣃࢱ࣮ࣥࡀྍ⬟ ⮬ᐙ㊊ሙᮦᩱࡢ㛤Ⓨ ᝈ⪅⣽⬊⏤᮶ࡢከᏍ㉁ᮦᩱ 㸦⮬ᐙ㊊ሙᮦᩱ㸧 ᝈ⪅ࡢ⣽⬊ ⣽⬊ 㗪ᆺ ⣽⬊ ࣐ࢺࣜࢵࢡࢫ ⬺⣽⬊ ࣐ࢺࣜࢵࢡࢫᮦᩱ 㸦⮬ᐙ㊊ሙᮦᩱ㸧 㗪ᆺ 㝖ཤ እほ 6(0┿ 7(0┿ ࢥ࣮ࣛࢤࣥࡢචᰁⰍീ Collagen 100 nm 100 μm ᴟࡵ࡚㧗࠸⏕యぶᛶ㸸⅖ᛂࡀ࡞࠸ࠊචᛂࡀ࡞࠸ ⏕య྾ᛶྜᡂ㧗ศᏊኳ↛㧗ศᏊࡢ」 」ྜᢏ⾡ ⏕య྾ᛶྜᡂ㧗ศᏊ 㸦PLLA, PGA, PLGA) ᙉᗘ ۑ ⏕యぶᛶ ⏕య྾ᛶኳ↛㧗ศᏊ (ࢥ࣮ࣛࢤࣥ㸧 ᙉᗘ ⏕యぶᛶۑ 」ྜ㊊ሙᮦᩱ 」ྜ ⏕య྾ᛶྜᡂ㧗ศᏊ࣓ࢵࢩࣗ ᙉᗘ ۑ ⏕యぶᛶۑ 」ྜ࣓ࢵࢩࣗ 」ྜ ⏕య྾ᛶྜᡂ㧗ศᏊࢫ࣏ࣥࢪ ࢥ࣮ࣛࢤࣥ ࢫ࣏ࣥࢪ 」ྜࢫ࣏ࣥࢪ 」ྜ 」ྜᢏ⾡㸸ẼᏍ⋡㐃㏻ᛶࡀ㧗ࡃࠊ⏕యぶᛶඃࢀࡓࢥ࣮ࣛࢤࣥࢫ࣏ࣥࢪࢆࠊ㧗࠸ຊᏛᙉᗘࢆ ࡶࡘྜᡂ㧗ศᏊࡢ㦵᱁㸦࣓ࢵࢩࣗࡸࢫ࣏ࣥࢪ㸧ᑟධࡍࡿ ࣓ࢵࢩࣗ≧ࡢ」ྜከᏍ㉁ᮦᩱࡢస〇᪉ἲ 3/*$ࢽࢵࢺ࣓ࢵࢩࣗ ࢥ࣮ࣛࢤࣥ Ỉ⁐ᾮࢆሬᕸ 3/*$ࢥ࣮ࣛࢤࣥ 」ྜ࣓ࢵࢩࣗ 㝽㛫ࢆࢥ࣮ࣛࢤࣥ Υ࡛⤖ Ỉ⁐ᾮ࡛‶ࡓࡋࡓ 3/*$ࢽࢵࢺ࣓ࢵࢩࣗ ࢥ࣮ࣛࢤࣥ Ỉ⁐ᾮࢆ ⤖ ⤖⇱ ࢢࣝࢱࣝࣝࢹ ࢢࣜࢩࣥỈ⁐ᾮ࡛ฎ⌮ࠊ ࣄࢻ࢞ࢫ࡛ฎ⌮ࠊ ᐊ ࠊ㛫 ࢥ࣮ࣛࢤࣥ ࢥ࣮ࣛࢤࣥ Υࠊ㛫 ࢫ࣏ࣥࢪᙧᡂ ࢫ࣏ࣥࢪࢆᯫᶫ ᮍᛂࡢࣝࢹࣄࢻ ᇶࢆࣈࣟࢵ࢟ࣥࢢ 3/*$ࢽࢵࢺ࣓ࢵࢩࣗࡢ⥙┠ࡢ✵㝽ࢥ࣮ࣛࢤࣥࡢ࣐ࢡࣟࢫ ࣏ࣥࢪࢆᙧᡂࡋࠊ3/*$ࢥ࣮ࣛࢤࣥ」ྜ࣓ࢵࢩࣗࢆ㛤Ⓨࡋࡓࠋ 」ྜࡼࡿከᏍ㉁ᮦᩱࡢᶵ⬟ྥୖ 㟼ⓗࣖࣥࢢ⋡(MPa) 」ྜࡼࡿຊᏛᙉᗘࡢྥୖ 40 3/*$࣓ࢵࢩࣗ 」ྜ࣓ࢵࢩࣗ 」ྜࡼࡿ⣽⬊᥋╔ࡢಁ㐍 ㌾㦵⣽⬊ 30 20 10 ࢥ࣮ࣛࢤࣥ 0 」ྜ࣓ࢵࢩࣗࡣࢥ࣮ࣛࢤࣥࢫ࣏ࣥࢪࡼࡾ ᩘⓒಸ㧗࠸ᙉᗘࢆ᭷ࡋࡓࠋ 」ྜ࣓ࢵࢩࣗࡣඃࢀࡓ⏕యぶᛶࢆ♧ࡋࡓࠋ ᚑ᮶ࡢከᏍ㉁㊊ሙᮦᩱࡢẚ㍑ ࢪ㸦᯾♫㸧 ࢥ࣮ࣛࢤࣥࢫ࣏ࣥࢪ㸦᯾♫㸧 㛗ᡤ㸸 㧗࠸ẼᏍ⋡ ▷ᡤ㸸 㒊ศⓗ㛢ሰࡋࡓ ⾲㠃✵Ꮝࠊ ప࠸ຊᏛᙉᗘ ࣂࢡ࣓ࣜࣝࢵࢩࣗ(ࢪࣙࣥࢯ࣭࢚ࣥ ࣥࢻ࣭ࢪࣙࣥࢯࣥᰴᘧ♫ࠊ⡿ᅜ) 1 mm 0,7ࡀ㛤Ⓨࡋࡓᮦᩱ㸦⡿ᅜ㸧Nature Materials (2007) ᚑ ᮶ ࡢ ᮦ ᩱ 㛗ᡤ㸸 㧗࠸ຊᏛᙉᗘࠊ ྲྀࡾᢅ࠸ࡸࡍ࠸ ▷ᡤ㸸 㝽㛫ࡀࡁࡃ ࡚⣽⬊ࡀ₃ࢀࡿࠊ 㧗ศᏊࡢྜࡣ㧗࠸ 㛗ᡤ㸸㧗࠸ຊᏛᙉᗘࠊྲྀࡾᢅ࠸ࡸࡍ࠸ ▷ᡤ㸸ẼᏍ⋡ࡣప࠸ࠊ㧗ศᏊࡢྜࡣ㧗࠸ 㛗ᡤ㸸㛤࠸ࡓ⾲㠃ᵓ㐀ࠊ㧗ẼᏍ⋡ 㧗࠸⣽⬊✀⋡ࠊ㧗࠸ຊᏛᙉᗘ ࡁ࡞⤌⧊ࡢ⏕ࡀྍ⬟ 」ྜ࣓ࢵࢩࣗࡢ㌾㦵⤌⧊⏕ࡢᛂ⏝ ⏕ࡋࡓ࢘ࢩࡢ㛵⠇㌾㦵 ཌࡳ㸸200 μm ཌࡳ㸸1 mm ཌࡳ㸸㸶mm 3/*$ࢥ࣮ࣛࢤࣥ」ྜ࣓ࢵࢩࣗࢆ⏝࠸࡚ࡁ࡞㛵⠇㌾㦵⤌⧊ࡢ⏕ᡂຌࠊ ⏕㌾㦵ࡣ⮬↛㌾㦵ࡢຊᏛᙉᗘ᭱ࡶ㏆ࡗࡓࠋ 」ྜ࣓ࢵࢩࣗࢆ⏝࠸ࡓ⓶⤌⧊ࡢ⏕ After implantation 100X +(ᰁⰍ After 2 weeks 40X 」ྜ㊊ሙᮦᩱࡼࡿ✀ࠎࡢᙧ≧ࡢ㦵ࡢ⏕ Bone knot Phalanx-like bone ከᏍ㉁㊊ሙᮦᩱࡢ ⤌⧊⏕ࡢᛂ⏝ Tissue Engineering Cartilage Bone ue ring s e s e i n T ngi sues E e is u Osteochondral Tiss ered T ine Tissue ing Eng r e e ngin E e Skin sues u s s i s i T T d eere n i g ring e e En n i Eng e u ues Tendon s s s s i i T ed T r e e ring e ngin e n ELigament i s Eng e u ssue i Muscle iss T T ered ring e n i Eng inee s g n Blood vessel ue E Tissue s s i T ered issues Nerve e n i Eng ered T ring ine Esophagus e g e n n i E Eng BladderTissues Engineered ࣓ࢹ࢝ࣝࢹࣂࢫࡢ,R7ࣉࣟࢪ࢙ࢡࢺࡢࡓࡵࡢ ㄪᰝ◊✲ ≀ᮦᶵᵓ0$1$㝞ᅜᖹ㸪ᮾ㝔ᕤ∵⏣ከຍᚿ㸪⏘⥲◊ே㛫ሗර⸨⾜ᚿ 㸯㸬⫼ᬒ ࣭ኻࢃࢀࡓ⏕య⤌⧊ࡢᶵ⬟ࢆ⏕ࡍࡿ ࣓ࢹ࢝ࣝࢹࣂࢫὀ┠㞟ࡲࡿ㸬 ࣭⏕⎔ቃࡢሗࡀ༑ศ㸬 㸰㸬┠ᶆ ࣓ࢹ࢝ࣝࢹࣂࢫෆእࡢ⤌⧊⏕⎔ ቃࢹ࣮ࢱࡢㄞྲྀ⤫ྜࢆྍ⬟ࡍࡿ ࢩࢫࢸ࣒ࡢ㛤Ⓨ ⤌⧊࣭⮚ჾࡢࢱ࣮ࢤࢵࢺ⤠ࡾ㎸ࡳ ࠙,R7ࠚ࣓ࢹ࢝ࣝࢹࣂࢫస〇㸩 ⣽⬊ᶵ⬟ไᚚ㸩⤌⧊⏕ሗࡢㄞྲྀ ࠙ࢹ࣮ࢱฎ⌮ࠚ࣓ࢹ࢝ࣝࢹࣂ ࢫෆእࡢ⤌⧊⏕⎔ቃ㛵ࡍࡿࢹ ࣮ࢱㄞྲྀ⤫ྜ 㸱㸬ಖ᭷ᢏ⾡ ࣭࣓ࢹ࢝ࣝࢹࣂࢫᢏ⾡㸦≀ᮦᶵᵓ㸧 ࣭⣽⬊ᶵ⬟ไᚚᢏ⾡㸦ᮾ㸧 ࣭ࣂ࢜ࢭࣥࢩࣥࢢᢏ⾡㸦⏘⥲◊㸧 ,R7࣓ࢹ࢝ࣝࢹࣂࢫ ⤌⧊⏕⎔ቃሗ ⤫ྜࢹ࣮ࢱ