㦵⏕་⒪⏝࠸ࡿ⏕యᮦᩱࡢ⾲㠃ᛶ≧ࡢ
᭱㐺㛵ࡍࡿ◊✲
The surface property optimizations of biomaterials used in bone tissue engineering
2013 ᖺ 7 ᭶
᪩✄⏣ᏛᏛ㝔 㐀⌮ᕤᏛ◊✲⛉
ᆅ⌫࣭⎔ቃ㈨※⌮ᕤᏛᑓᨷ ᛂ⏝㖔≀Ꮫ◊✲
⛬
Kan CHENG
The Surface Property Optimizations of Biomaterials used in Bone Tissue Engineering
Kan Cheng
Abstract
The surface property of artificial bone, percutaneous device and other biomaterials (scaffold) has received much attention in recent years owing to the effect on cellular functions, including adhesion, proliferation and differentiation. However, the correlation remains unclear between scaffold and cell morphologies of biomaterials, particularly cell attachment area of MSCs in the initial stage of culturing. In this study, ceramic and metal biomaterials are selected which are often used in bone tissue engineering and the surface properties of these biomaterials are discussed thus to further develop prediction technology of cell functions on various type of biomaterials. The detail topics include (1) an non-absorbent ȕ-tricalcium phosphate/hydroxyapatite disk (HAp/TCP); (2)various surface properties of hydroxyapatite disk (HAp);(3)a hydroxyapatite layer on titanium(Ti) or oxidized titanium (TiO2). Chapter two also emphasized that apatite layers were fixed immovably on oxidized titanium thus proteins were successfully immobilized.
This article is composed of six chapters.
First chapter is focused on research background and summaries especially experimental methods in the research. In order to reveal the correlation between cell functionality and biomaterials, or cell adhesion morphology and cell differentiation in initial stage, understanding the form of cell initial contacts on biomaterials becomes critical. For cell adhesion morphological of biomaterials in its initial stage, visualization techniques and evaluation techniques were specially developed. Applying techniques described above is for exploring correlation of cell functionalities of biomaterials and expecting to develop predictive technology of cell differentiation according to contact areas of cell initial formation. For the types of biomaterials such as metal, ceramic, etc.,
their surface properties will be adjusted via physical or chemical treatment such as heat process or acid treatment, etc., so that to systemically study modification of cell morphology and cell differentiation.
Second chapter describes a two-step method to fabricate a fibroblast growth factor (FGF)-2/ apatite composite layer and to immobilize FGF-2 on anodically oxidized titanium pins at room temperature. Anodically oxidized titanium pins pre-coated with a homogeneous apatite layer were immersed in a supersaturated calcium phosphate solution containing FGF-2 at 25Υ for 24 hours. The contents of FGF-2 on the FGF-2-apatite composite layer were found to be 0.41±0.12 ȝg/cm2. The FGF-2 was immobilized not by adsorption but by co-precipitation with apatite on the titanium pins.
Third chapter describes the correlation between cell attachment areas after 2 hours of culture and osteogenic differentiation activity of rat mesenchymal stem cells (rMSCs) on non-absorbent ȕ-tricalcium phosphate/hydroxyapatite disk (HAp/TCP). The results illustrate that the ȕ-TCP particles on disk surface and the characteristics of collection from hydroxyapatite particles may affect the cell attachment areas in initial stage cultured on a surface of materials and also osteogenic differentiation activity. In summary, optimization of the surface condition on non-absorbent TCP/HAp material was established.
Forth chapter focused on the correlation between cell attachment areas after 2 hours of culture and osteogenic differentiation activity of rat mesenchymal stem cells (rMSCs) on various surfaces of hydroxyapatite disks (HAp). Involving ceramic raw material and hydroxyapatite powder, present study demonstrates that a wide range of crystal grain size distribution and surface of fine structure on apatite disks can be manufactured systematically depending on various types of sintered temperatures.
Further, on these type surfaces of hydroxyapatite disks sowing rMSCs, a correlation was established between cell attachment area in the initial stage and osteogenic differentiation activity in the culture after 3 weeks. In particular, a correlation is determined between the hydroxyapatite particle sizes of the disk surface and the cell attachment area. The results showed that the smaller cell attachment area usually the higher the osetogenic differentiation activity.
Fifth chapter is for correlation between cell attachment areas after 2 hours of
culture and ostrogenic differentiation activity of rat mesenchymal stem cells (rMSCs) on a hydroxyapatite layer of titanium(Ti) or oxidized titanium (TiO2). After immersion in the supersaturated calcium phosphate solution, apatite layers synthesized Ti, H2O2-Ti, and 300ºC-Ti plates. By identifying these different types of morphological, and chemical, and/or structural characteristics, the correlation between cell attachment areas and ostrogenic differentiation activity is determined. Finally, this chapter describes the technical feasibility of cell differentiation and forecast on biomaterials.
Last Chapter summarized conclusion of the study and the future direction of development.
࣭Abstract
➨ 㸯 ❶ ⥴ ㄽ ... 1
1.1 ⫼ ᬒ ࣭ ┠ ⓗ ... 1
1.2 ࡞ ᮦ ᩱ ศ ᯒ ᪉ ἲ ... 7
1.2.1 ㉮ ᰝ 㟁 Ꮚ 㢧 ᚤ 㙾 ... 7
1.2.2 ⷧ ⭷ X ⥺ ᅇ ᢡ ... 7
1.3 ⣽ ⬊ ... 8
1.3.1 㛫 ⴥ ⣔ ᖿ ⣽ ⬊(mesenchymal stem cell) ... 8
1.3.2 ࡞ ⣽ ⬊ ほ ᐹ ᪉ ἲ ... 9
1.3.3 ⣽ ⬊ ึ ᮇ ᥋ ╔ ᙧ ែ ࡢ ⏬ ീ ᢏ ⾡ ... 9
1.3.4 ゎ ᯒ ᡭ 㡰... 10
1.3.5 ⣽ ⬊ ึ ᮇ ᥋ ╔ 㠃 ✚ ... 11
➨ 2 ❶ 㝧 ᴟ 㓟 ࢳ ࢱ ࣥ ࣆ ࣥ ୖ ࡢ ⧄ ⥔ ⱆ ⣽ ⬊ ᡂ 㛗 ᅉ Ꮚ(FGF)-2/ ࣃ ࢱ ࢺ 」 ྜ ᒙ ࡢ ᙧ ᡂ ... 12
2.1 ⥴ ゝ ... 12
2.1.1 ◊ ✲ ┠ ⓗ... 12
2.1.2 ◊ ✲ ⫼ ᬒ... 13
2.1.3 እ 㦵 ᢡ ᅛ ᐃ ... 14
2.1.3.1 እ 㦵 ᢡ ᅛ ᐃ ࡣ ... 14
2.1.3.2 እ 㦵 ᢡ ᅛ ᐃ ჾ ල ... 15
ࢳ ࢱ ࣥ ࢫ ࢡ ࣜ ࣗ ࣮ ࠊ እ 㦵 ᢡ ᅛ ᐃ ჾ ࡢ ✀ 㢮 ࠊ እ ᅛ ᐃ ἲ ࡢ 㛗 ᡤ ▷ ᡤࠊ እ ᅛ ᐃ ἲ ࡢ 㐺 ᛂ ࠊ ྜ ే 2.1.4 㦵 ࡢ ಟ ... 18
2.1.4.1 㦵 ᢡ ࡢ ⒵ ... 18
2.1.4.2 ୍ ḟ ᛶ 㦵 ⒵ ྜ ... 19
2.1.4.3 㦵 ᢡ ⒵ ᙳ 㡪 ࢆ ཬ ࡰ ࡍ ᅉ Ꮚ ... 19
2.1.5 ࢱ ࣥ ࣃ ࢡ 㸫 ࣜ ࣥ 㓟 ࢝ ࣝ ࢩ ࢘ ࣒ ඹ ỿ ᢸ ᣢ ἲ ... 20
2.1.5.1 ࣜ ࣥ 㓟 ࢝ ࣝ ࢩ ࢘ ࣒ 㐣 㣬 ⁐ ᾮ ... 20
2.1.5.2 ⧄ ⥔ ⱆ ⣽ ⬊ ᡂ 㛗 ᅉ Ꮚ(FGF-2) ... 21
2.2 ⁐ ᾮ ཬ ࡧ ホ ౯ ᪉ ἲ ... 22
2.2.1 ⁐ ᾮ ... 22
2.2.1.1 ྵ ࢝ ࣝ ࢩ ࢘ ࣒ ⁐ ᾮ ... 22
ࣜ ࣥ ࢤ ࣝ ᾮ(Ringer ’s Solution)ࠊ
ࢥ ࣥ ࢡ ࣛ ࢺ 㸫Ca ᾮ(Conclyte-Ca Solution)
2.2.1.2 ྵ ࣜ ࣥ ⁐ ᾮ ... 23
ࢡ ࣜ ࢽ ࢨ ࣝ ࢶ B(Klinisalz B)ࠊ ࢯ ࣜ ࢱ 㸫T2(SOLITA-TNo.2) ࢥ ࣥ ࢡ ࣛ ࢺ ᾮ 㸫PK(Conclyte-PK Solution) 2.2.1.3 pH ㄪ ᩚ ... 26
ࣂ ࣇ ࣝ(Bifil)ᑓ ⏝ Ⅳ 㓟 Ỉ ⣲ ࢼ ࢺ ࣜ ࢘ ࣒ ⿵ ᾮ ࠊ ࣓ ࣟ ࣥ ᾮ(Meylon Solution) 2.2.1.4 ࡑ ࡢ ... 27
ࣇ ࣈ ࣛ ࢫ ࢺ ࢫ ࣉ ࣞ ࣮500 ⏕ ⌮ ⓗ 㣗 ሷ Ỉ(physiological salt solution) 2.2.2 ホ ౯ ᪉ ἲ... 28
2.2.2.1 ㉮ ᰝ 㟁 Ꮚ 㢧 ᚤ 㙾 ... 28
ཎ ⌮ ࠊ ほ ᐹ ᮲ ௳ 2.2.2.2 ㄏ ᑟ ⤖ ྜ ࣉ ࣛ ࢬ ࣐ Ⓨ ග ศ ᯒ ⨨ ... 29
ཎ ⌮ ࠊ ᐃ ᮲ ௳ ࠊ ᳨ 㔞 ⥺ 2.2.2.3 ⣸ እ ྍ ど ศ ග ග ᗘ ィ ... 30
ཎ ⌮ ࠊ ᐃ ᮲ ௳ ࠊ ᳨ 㔞 ⥺ 2.2.2.4 ⢊ ᮎ X ⥺ ᅇ ᢡ ... 31
ཎ ⌮ ࠊ ᐃ ᮲ ௳ 2.3 ་ ⒪ ⏝ ㍺ ᾮ ΰ ྜ ⁐ ᾮ ࡢ ࣜ ࣥ 㓟 ࢝ ࣝ ࢩ ࢘ ࣒ ᙧ ᡂ ⬟ ホ ౯ ... 32
2.3.1 ᐇ 㦂 ┠ ⓗ... 32
2.3.2 ᐇ 㦂 ᧯ స... 32
2.3.2.1 ࣃ ࣛ ࣓ ࣮ ࢱ ࡘ ࠸ ࡚ ... 32
ᇶ ᮏ ᆺ ࡢ ΰ ྜ ἲ ࠊ Ⓨ ᒎ ᆺ ࡢ ΰ ྜ ἲ 2.3.2.2 ΰ ྜ ᮲ ௳ ... 35
ᇶ ᮏ ᆺ ࠊ Ⓨ ᒎ ᆺ 2.3.2.3 ᐇ 㦂 ᡭ 㡰 ... 38
2.3.3 ᐇ 㦂 ⤖ ᯝ... 39
2.3.3.1 pH ᐃ ࢹ ࣮ ࢱ ཬ ࡧ pH ᅗ ... 39
2.3.3.2 ICP ࢹ ࣮ ࢱ ཬ ࡧ ICP ᅗ ... 45
ICP ࢹ ࣮ ࢱ ཬ ࡧ ᅗ(37Υ)ࠊICPࢹ ࣮ ࢱ ཬ ࡧ ᅗ(50Υ) 2.3.4 ⪃ ᐹ ... 49
2.3.4.1 pH ᅗ ࡘ ࠸ ࡚ ... 49
2.3.4.2 ICP ࢹ ࣮ ࢱ ࡘ ࠸ ࡚ ... 50
2.3.4.3 ࣃ ࣛ ࣓ ࣮ ࢱ ࡘ ࠸ ࡚ ... 50
2.4 㝧 ᴟ 㓟 Ti Წ ࡢ ࣜ ࣥ 㓟 ࢝ ࣝ ࢩ ࢘ ࣒ ࢥ ࣮ ࢸ ࣥ ࢢ ᒙ ... 52
2.4.1 ᐇ 㦂 ┠ ⓗ... 52
2.4.2 ᐇ 㦂 ᧯ స... 52
2.4.2.1 ᇶ ᮦ ࡘ ࠸ ࡚ ... 52
2.4.2.2 ࣜ ࣥ 㓟 ࢝ ࣝ ࢩ ࢘ ࣒ 㐣 㣬 ⁐ ᾮ ฎ ⌮ ... 53
2.4.3 ᐇ 㦂 ⤖ ᯝ... 53
2.4.3.1 Ti Წ ୖ ࡢ ࣜ ࣥ 㓟 ࢝ ࣝ ࢩ ࢘ ࣒ ࡢ ᯒ ฟ 㔞 ... 54
2.4.3.2 SEM ┿ ཬ ࡧ EDX ⤖ ᯝ ... 56
SEM ┿ ཬ ࡧ EDX ⤖ ᯝ ࢢ ࣛ ࣇ ࠊ EDX ࢫ ࣌ ࢡ ࢺ ࣝ ࡢ ࣆ ࣮ ࢡ 㠃 ✚ ᙉ ᗘ ẚ 2.4.4 ⪃ ᐹ ... 85
2.5 㝧 ᴟ 㓟 Ti Წ ࡢ FGF-2㸫 ࣜ ࣥ 㓟 ࢝ ࣝ ࢩ ࢘ ࣒ ᒙ ᙧ ᡂ ... 86
2.5.1 ᐇ 㦂 ┠ ⓗ... 86
2.5.2 ᐇ 㦂 ᧯ స... 86
2.5.3 ᐇ 㦂 ⤖ ᯝ... 87
2.5.4 ⪃ ᐹ ... 95
2.6 FGF-2 ᢸ ᣢ ࡼ ࡿ ⣽ ⬊ ά ᛶ ホ ౯ ... 98
2.6.1 ᐇ 㦂 ┠ ⓗ... 98
2.6.2 ᐇ 㦂 ᧯ స... 98
2.6.1.1 Ti ࢫ ࢡ ࣜ ࣗ ࣮ ࡘ ࠸ ࡚ ... 98
2.6.2.2 ᐇ 㦂 ᡭ 㡰 ... 98
RKB ᾮ ࢆ ⏝ ࡋ ࡓ ࢥ ࣥ ࢺ ࣟ ࣮ ࣝ ࡢ స 〇 ࠊ FGF-2 ᢸ ᣢ Ti ࢫ ࢡ ࣜ ࣗ ࣮ ࡢ స 〇 ࠊFGF-2 ࡢ ᢳ ฟ ࠊ ⣽ ⬊ ᐇ 㦂 ࡼ ࡿ FGF-2 ࡢ ά ᛶ ホ ౯ ᪉ ἲ 2.6.3 ᐇ 㦂 ⤖ ᯝ... 107
2.6.3.1 FGF-2 ᢸ ᣢ 㔞 ... 107
2.6.3.2 ICP ࢹ ࣮ ࢱ ཬ ࡧ ICP ᅗ ... 108
2.6.3.3 ⣽ ⬊ ࡼ ࡿ FGF-2 ά ᛶ ホ ౯ ... 110
2.6.3.4 ⣽ ⬊ ┿ ... 112
2.6.4 ⪃ ᐹ ... 116
➨ 3 ❶ 㠀 ྾ ᛶ ȕ-TCP ྵ ᭷ ࣃ ࢱ ࢺ ࢹ ࢫ ࢡ ୖ ࠾ ࡅ ࡿ ࣛ ࢵ ࢺ ⏤ ᮶ 㛫 ⴥ ⣔ ᖿ ⣽ ⬊ ึ ᮇ ᥋ ╔ ᣲ ື ཬ ࡧ ⣽ ⬊ ศ ⬟ ࡢ ┦ 㛵 ... 118
3.1 ᐇ 㦂 ┠ ⓗ ... 118
3.2 ᐇ 㦂 ᮦ ᩱ ... 118
3.3 ᐇ 㦂 ⤖ ᯝ ... 118 3.3.1 㠀 ྾ ᛶ ȕ-TCP ྵ ᭷ ࣃ ࢱ ࢺ ࢹ ࢫ ࢡ ୖ ࡛ ࡢ ࣛ ࢵ ࢺ ⏤ ᮶ 㛫 ⴥ ⣔
ᖿ ⣽ ⬊(rMSCs)⏕ Ꮡ ⋡ ཬ ࡧ ึ ᮇ ᥋ ╔ 㠃 ✚ ... 118
3.3.2 㠀 ྾ ᛶ ȕ-TCP ྵ ᭷ ࣃ ࢱ ࢺ ࢹ ࢫ ࢡ ୖ ࡛ ࡢ DNA ⃰ ᗘ .... 121
3.3.3 㠀 ྾ ᛶ ȕ-TCP ྵ ᭷ ࣃ ࢱ ࢺ ࢹ ࢫ ࢡ ୖ ࡛ ࡢ 㦵 ᙧ ᡂ ศ ⬟ 122 3.3.4 㛫 ⴥ ⣔ ᖿ ⣽ ⬊ ࡢ ึ ᮇ ᥋ ╔ 㠃 ✚ ཬ ࡧ 㦵 ศ ⬟ ࡢ ┦ 㛵 ... 123
3.4 ⪃ ᐹ ... 124
➨ 4 ❶ ␗ ࡞ ࡿ ᚤ ⣽ ᵓ 㐀 ࢆ ᭷ ࡍ ࡿ ࣃ ࢱ ࢺ ࢹ ࢫ ࢡ ୖ ࠾ ࡅ ࡿ ࣛ ࢵ ࢺ ⏤ ᮶ 㛫 ⴥ ⣔ ᖿ ⣽ ⬊(rMSCs)ึ ᮇ ᥋ ╔ ᣲ ື ཬ ࡧ ⣽ ⬊ ศ ⬟ ࡢ ┦ 㛵 ... 126
4.1 ᐇ 㦂 ┠ ⓗ ... 126
4.2 ᐇ 㦂 ᮦ ᩱ ... 126
4.3 ᐇ 㦂 ⤖ ᯝ ... 126
4.3.1 ࣃ ࢱ ࢺ ࢹ ࢫ ࢡ ࡢ ≀ ᛶ ホ ౯ ... 127
SEM ほ ᐹ ཬ ࡧ ⷧ ⭷ X ⥺ ᅇ ᢡ ࣃ ࢱ ࣮ ࣥ ࢆ ⏝ ࠸ ࡓ ✀ ࠎ ࣃ ࢱ ࢺ ࢹ ࢫ ࢡ ࡢ ⾲ 㠃 ᛶ ≧ ศ ᯒ ࣃ ࢱ ࢺ ࢹ ࢫ ࢡ ࡢ PBS(-)ᾐ ₕ ᾮ ࡢ pH ್ ࣃ ࢱ ࢺ ࢹ ࢫ ࢡ ࡽ ࡢ ࢝ ࣝ ࢩ ࢘ ࣒ ⁐ ゎ 㔞 4.3.2 ࣃ ࢱ ࢺ ࢹ ࢫ ࢡ ୖ ࡛ ࡢ ࣛ ࢵ ࢺ 㛫 ⴥ ⣔ ᖿ ⣽ ⬊ ึ ᮇ ᥋ ╔ ᙧ ែ . 132 ↓ ⾑ Ύ ᇵ ᆅ ࡛ 2 㛫 ᇵ 㣴 ᚋ ࡢ ⣽ ⬊ ᥋ ╔ 㠃 ✚ 4.3.3 ࣃ ࢱ ࢺ ࢹ ࢫ ࢡ ୖ ࡛ ࡢ ⣽ ⬊ ศ ⬟ ... 136
␗ ࡞ ࡿ ᚤ ⣽ ᵓ 㐀 ࢆ ᭷ ࡍ ࡿ ࣃ ࢱ ࢺ ࢹ ࢫ ࢡ ୖ ࡛ ࡢ DNA ⃰ ᗘ ࣃ ࢱ ࢺ ࢹ ࢫ ࢡ ୖ ࡛ ࡢ ࢜ ࢫ ࢸ ࢜ ࢝ ࣝ ࢩ ࣥ ྵ ᭷ 㔞 ␗ ࡞ ࡿ ᚤ ⣽ ᵓ 㐀 ࢆ ᭷ ࡍ ࡿ ࣃ ࢱ ࢺ ࢹ ࢫ ࢡ ୖ ࡢ 㛫 ⴥ ⣔ ᖿ ⣽ ⬊ ึ ᮇ ᥋ ╔ 㠃 ✚ ཬ ࡧ 㦵 ᙧ ᡂ ศ ⬟ ࡢ ┦ 㛵 ᛶ 4.4 ⪃ ᐹ ... 138
➨ 5 ❶ ࣃ ࢱ ࢺ ᒙ ࡛ ⾲ 㠃 ಟ 㣭 ࡋ ࡓ ࢳ ࢱ ࣥ ୖ ࠾ ࡅ ࡿ 㛫 ⴥ ⣔ ᖿ ⣽ ⬊ ึ ᮇ ᥋ ╔ ᣲ ື ཬ ࡧ ⣽ ⬊ ศ ⬟ ࡢ ┦ 㛵 ... 141
5.1 ᐇ 㦂 ┠ ⓗ ... 141
5.2 ᐇ 㦂 ᪉ ἲ ... 141
5.3 ᐇ 㦂 ⤖ ᯝ ... 141
5.3.1 ✀ ࠎ ࡢ ࣃ ࢱ ࢺ ᒙ ࡛ ⾲ 㠃 ಟ 㣭 ࡋ ࡓ ࢳ ࢱ ࣥ ᯈ ࡢ ≀ ᛶ ホ ౯ ... 142
✀ ࠎ ࡢ ࣃ ࢱ ࢺ ᒙ ࡛ ⾲ 㠃 ಟ 㣭 ࡋ ࡓ ࢳ ࢱ ࣥ ᯈ ࡢ SEM ほ ᐹ ✀ ࠎ ࡢ ࣃ ࢱ ࢺ ᒙ ࡛ ⾲ 㠃 ಟ 㣭 ࡋ ࡓ ࢳ ࢱ ࣥ ࡢ ⷧ ⭷ X ⥺ ᅇ ᯒ ศ ᯒ 5.3.2 ✀ ࠎ ࡢ ࣃ ࢱ ࢺ ᒙ ࡛ ⾲ 㠃 ಟ 㣭 ࡋ ࡓ ࢳ ࢱ ࣥ ୖ ࡛ ࡢ 㛫 ⴥ ⣔ ᖿ ⣽ ⬊ ࡢ ึ ᮇ ᥋ ╔ 㠃 ✚ ... 145
5.3.3 ✀ ࠎ ࡢ ࣃ ࢱ ࢺ ᒙ ࡛ ⾲ 㠃 ಟ 㣭 ࡋ ࡓ ࢳ ࢱ ࣥ ୖ ࡛ ࡢ 㦵 ᙧ ᡂ ศ ⬟ ... 147 5.3.4 ✀ ࠎ ࡢ ࣃ ࢱ ࢺ ᒙ ࡛ ⾲ 㠃 ಟ 㣭 ࡋ ࡓ ࢳ ࢱ ࣥ ୖ ࡛ ࡢ 㛫 ⴥ ⣔ ᖿ ⣽ ⬊ ึ
ᮇ ᥋ 㠃 ✚ ཬ ࡧ 㦵 ᙧ ᡂ ศ ⬟ ࡢ ┦ 㛵 ... 148 5.4 ⪃ ᐹ ... 149
➨ 6 ❶ ⤖ ㄽ ... 151
࣭ ㅰ ㎡
࣭ ཧ ⪃ ᩥ ⊩
࣭ ཧ ⪃ ㈨ ᩱ
࣭ ◊ ✲ ᴗ ⦼
1
➨ 1 ❶ ⥴ㄽ 1.1 ⫼ ᬒ ࣭ ┠ ⓗ
ᖿ ⣽ ⬊ ➼ ࠊ⏕ ࡁ ࡓ ⣽ ⬊ ࢆ ⏝ ࠸ ࡿ ⏕ ་ ⒪ ࡣ ࠊᚑ ᮶ ᆺ ࡢ ᑐ ฎ ⒪ ἲ ⓗ ⒪ ᢏ
⾡ ࡣ ␗ ࡞ ࡾ ࠊ⤌ ⧊ ⏕ ࡼ ࡾ ᵓ 㐀࣭ᶵ ⬟ ࢆ ᅇ ࡉ ࡏ ࡿ ඛ ➃ ⓗ ᰿ ᢏ ⾡ ࡛
࠶ ࡿ ࠋ⤌ ⧊ ࢆ ⏕ ࡍ ࡿ ࡓ ࡵ ࡣ ࠊ⣽ ⬊ ࢆ ᧯ స ࣭ ຍ ᕤ ࡋ ࡓ ᚋ ࠊᝈ ⪅ ᵝ ᡠ ࡍ
ࣉ ࣟ ࢭ ࢫ ࡀ ᚲ せ ࡞ ࡿ ࡀ ࠊ ࡃ ᪂ ࡋ ࠸ ⒪ ᢏ ⾡ ࡛ ࠶ ࡿ ࡓ ࡵ ࠊྛ ẁ 㝵 ࡛ ࡢ ⣽
⬊ ࣭ ⤌ ⧊ ࡢ ホ ౯ ᪉ ἲ ࡢ ☜ ❧ ࡀ ồ ࡵ ࡽ ࢀ ࡚ ࠸ ࡿ ࠋࡲ ࡓ ࠊ ⏕ ་ ⒪ ࡣ ࠊ㠀 ᖖ ᪂ つ ᛶ ࡢ 㧗 ࠸ ศ 㔝 ࡛ ࠶ ࡿ ࡀ ࡺ ࠼ ࠊ᪤ Ꮡ ࡢ ホ ౯ ᪉ ἲ ࡀ ᙺ ❧ ࡓ ࡓ ࡞ ࠸ ሙ ྜ ࡀ ከ ࡃ ࠊࡑ ࡢ ሙ ྜ ࠊ᪂ ࡓ ホ ౯ ᪉ ἲ ࢆ ᵓ ⠏ ࡋ ࡞ ࡅ ࢀ ࡤ ࡞ ࡽ ࡞ ࠸ ࠋ≉ ࠊ
ᴗ ࡢ ⤒ ῭ ⓗ ぢ ㏻ ࡋ ࢆ ᫂ ☜ ࡋ ࠊ ⏕ ་ ⒪ ࡢ ᐇ ⏝ ࢆ ᥎ 㐍 ࡍ ࡿ ࡓ ࡵ ࡣ ࠊ⣽
⬊/ ⏕ ⤌ ⧊ ࡀ ⛣ ᳜ ᮇ ᚅ ࡉ ࢀ ࡿ ᶵ ⬟ ࢆ ᭷ ࡋ ࡚ ࠸ ࡿ ࡇ ࢆ ࠊ ᇵ 㣴 ࡢ ึ ᮇ ẁ 㝵 ࡛ ண ホ ౯ ࣭ ุ ᐃ ࡍ ࡿ ᢏ ⾡ ࡀ ồ ࡵ ࡽ ࢀ ࡿ ࠋ
ᡃ ࡀ ᅜ ࡢ ⊂ ❧ ⾜ ᨻ ἲ ே ⏘ ᴗ ᢏ ⾡ ⥲ ྜ ◊ ✲ ᡤ(௨ ୗ ࠊ ⏘ ⥲ ◊)ࡢ ࣄ ࣗ ࣮ ࣐ ࣥ
ࣛ ࣇ ࢸ ࢡ ࣀ ࣟ ࢪ ࣮ 㧗 ᶵ ⬟ ⏕ య ᮦ ᩱ ◊ ✲ 㒊 㛛 ࡛ ࡣ ࠊ⌧ ≧ ࡢ ⏕ ་ ⒪ ࡢ ⤒ ῭
ⓗ ᢏ ⾡ ⓗ ၥ 㢟 ࢆ Ⓨ ᒎ ⓗ ゎ Ỵ ࡍ ࡿ ᪉ ἲ ࡋ ࡚ࠕ ⏕ య ෆ ᇙ ධ ࡍ ࡿ ᮦ ᩱ ⮬
㌟ ࡀ ⣽ ⬊ ศ ࡸ ⤌ ⧊ ⏕ ࢆ ಁ ࡀ ࡍ ࠖ➨ 3 ୡ ௦ ⏕ య ᮦ ᩱ ࡢ 㛤 Ⓨ ࢆ ࢸ ࣮ ࣐ ࡢ 㸯 ࡘ ࡋ ࡚ ◊ ✲ ࢆ ⾜ ࡗ ࡚ ࠸ ࡿ ࠋᮏ ◊ ✲ ࡣ ࠊ⏘ ⥲ ◊ ࡢ ඹ ྠ ◊ ✲ ࡼ ࡾ ࠊ⏕
య ᮦ ᩱ ࠾ ࡅ ࡿ ◊ ✲ ࢆ ⿵ ࠸ ࠊ⣽ ⬊ ⏕ ≀ Ꮫ ࡢ ど Ⅼ ࢆ ධ ࢀ ࡘ ࡘ ࠊ⼥ ྜ ࡋ ࡚ ୍ ᒙ ࡢ 㐍 ᒎ ࢆ ィ ࡿ ࡓ ࡵ ࠊࠕ 㦵 ⏕ ་ ⒪ ⏝ ࠸ ࡿ ⏕ య ᮦ ᩱ ࡢ ⾲ 㠃 ᛶ ≧ ࡢ ᭱ 㐺 㛵 ࡍ ࡿ ◊ ✲ ࠖ ࢆ ࢸ ࣮ ࣐ ࡋ ࡚ ◊ ✲ ࢆ ⾜ ࡗ ࡚ ࡁ ࡓ ᡂ ᯝ ࡛ ࠶ ࡿ ࠋ
⏕ య ᮦ ᩱ ศ 㔝 ࠾ ࠸ ࡛ ࠊࡑ ࡢ ⾲ 㠃 ᛶ ≧ ࡣ ࢀ ᛶ ࡸ ࠊᙧ ែ ࡸ ࠊᗄ ఱ ᙧ ≧
ࡸ ࠊᙎ ᛶ ࡸ ࠊ⁐ ゎ ᛶ ࡞ ࢆ ᣲ ࡆ ࡽ ࢀ ࡿ ࠋே ᕤ 㦵 ࡸ ⤒ ⓶ ࢹ ࣂ ࢫ ࡞ ࡢ ⏕ య
ᮦ ᩱ (⣽ ⬊ ࡢ ㊊ ሙ 㸪scaffold)ࡢ ⾲ 㠃 ᛶ ≧ ࡣ ⣽ ⬊ ࠊ≉ 㛫 ⴥ ⣔ ᖿ ⣽ ⬊(MSCs) ࡢ ศ ࡁ ࡃ ᙳ 㡪 ࢆ ࠼ ࡿ ࡇ ࡀ ࢃ ࡗ ࡚ ࡁ ࡓ ࠋ
ල య ⓗ ࡞ ෆ ᐜ ࢆ ᣲ ࡆ ࡿ ࠊࡲ ࡎ ࠊ⏕ య ᮦ ᩱ ⾲ 㠃 ࡢ ࢀ ᛶ ࡣ 㛫 ⴥ ⣔ ᖿ ⣽ ⬊ ࡢ ศ ᙳ 㡪 ࢆ ࠼ ࡿ ࡇ ࡀ ࢃ ࡗ ࡚ ࡁ ࡓ ࠋ
Olivares Navarrete[ 1 ]ࡽ ࡣ ࠊ ࢧ ࣥ ࢻ ࣈ ࣛ ࢫ ࢺ 㓟 ࢚ ࢵ ࢳ ࣥ ࢢ ฎ ⌮ ࡼ ࡾ ࢳ ࢱ ࣥ ᯈ ࡢ ๓ 㐍 ᥋ ゐ ゅ ࡀ 95.8° ࡽ 0°ࡲ ࡛ ῶ ᑡ ࡉ ࡏ ࠊ㉸ ぶ Ỉ ᛶ ࢆ ᣢ ࡘ ࢳ ࢱ ࣥ
ୖ ᇵ 㣴 ࡋ ࡓ MSCs ࡀ 㦵 ⱆ ⣽ ⬊ ศ ࡋ ࠊ㦵 ᙧ ᡂ ศ ⬟ ࢆ ಁ 㐍 ࡉ ࢀ ࡿ ࡇ
ࢆ ♧ ࡋ ࡓ ࠋAita[ 2 ]ࡽ ࡣ ࠊ⣸ እ ⥺ ฎ ⌮ ࡼ ࡾ ࢳ ࢱ ࣥ ᯈ ࡢ ᥋ ゐ ゅ ࡀ 90° ࡽ 10°
௨ ୗ ῶ ᑡ ࡉ ࡏ ࠊ㉸ ぶ Ỉ ᛶ ࡞ ࡗ ࡓ ࢳ ࢱ ࣥ ᯈ ≧ ୖ ࠾ ࡅ ࡿ MSCs ࡢ ᥋ ╔ ᛶ ཬ ࡧ 㦵 ᙧ ᡂ ศ ⬟ ࢆ ಁ 㐍 ࡉ ࢀ ࡿ ࡇ ♧ ࡋ ࡓ ࠋCurran[ 3 ]ࡽ ࡣ ࠊ ⬡ ⫫ ᪘ ࣏ ࣜ
࢚ ࢫ ࢸ ࣝ ࣏ ࣜ dž ࢝ ࣉ ࣟ ࣛ ࢡ ࢺ ࣥ(PCL) ࣏ ࣜ(ࣛ ࢡ ࢳ ࢻ-co-ࢢ ࣜ ࢥ ࣜ ࢻ)(PLGA)ࢆ ␗ ࡞ ࡿ ΰ ྜ ྜ ࡛ ⭷ ≧ ⏕ య ᮦ ᩱ ࢆ స ᡂ ࡋ ࠊ(80wt㸣
PCL+20wt㸣)ぶ Ỉ ⓗ ࡞ ⾲ 㠃 ᛶ ≧ ࢆ ᣢ ࡘ PLGA ୖ ࠾ ࡅ ࡿ MSCs ࡢ 㦵 ᙧ ᡂ ศ ⬟ ࢆ ಁ 㐍 ࡉ ࢀ ࡿ ࡇ ࢆ ♧ ࡋ ࡓ ࠋIviroco[ 4 ]ࡽ ࡣ ࠊCLMA-co-HEA ࡢ 3D
2
ከ Ꮝ య ࡀ HEA ྵ ᭷ 㔞 ࡼ ࡾ ㄪ ᩚ ࡛ ࡁ ࠊ30㸣HEA ࢆ ྵ ᭷ ࡍ ࡿ 3D ከ Ꮝ య ୖ ᇵ 㣴 ࡋ ࡓ MSCs ࡢ 㦵 ᙧ ᡂ ศ ⬟ ࢆ ಁ 㐍 ࡉ ࢀ ࡿ ࡇ ࢆ ♧ ࡋ ࡓ ࠋ
ࡲ ࡓ ࠊ⏕ య ᮦ ᩱ ⾲ 㠃 ୖ ಟ 㣭 ࡋ ࡓ ᐁ ⬟ ᇶ ཬ ࡧ ࢱ ࣥ ࣃ ࢡ ㉁ ࡣ ࢀ ᛶ ࢆ ኚ
࡛ ࡁ ࠊMSCs ࡢ ศ ᙳ 㡪 ࢆ ࠼ ࡿ ࡇ ࡀ ࢃ ࡗ ࡚ ࡁ ࡓ ࠋ
㸫CH3ࠊ 㸫OHࠊ 㸫COOHࠊ ཬ ࡧ 㸫NH2࡛ ಟ 㣭 ࡋ ࡓ ᮦ ᩱ ⾲ 㠃 ࡣ ⣽ ⬊ ᥋ ╔
ࣥ ࢸ ࢢ ࣜ ࣥ ࢆ ㄪ ᩚ ࡛ ࡁ ࠊ ⣽ ⬊ ࡢ ศ ࡞ ࡢ ᣲ ື ࢆ ኚ ࡉ ࡏ ࡿ[ 5 , 6 ]ࠋ Curran[ 7 , 8 ]ࡽ ࡣ 㸫NH2ࠊ㸫SH ࡛ ಟ 㣭 ࡋ ࡓ ࢞ ࣛ ࢫ(TAAB)ୖ MSCs ࢆ ᇵ 㣴 ࡋ ࠊ 㦵 ᙧ ᡂ ศ ⬟ ࢆ ಁ 㐍 ࡍ ࡿ ࡇ ࢆ ሗ ࿌ ࡋ ࡓ ࠋ ࡲ ࡓ ࠊBeroit[ 9 ]ࡽ ࡣ ࠊ ࣜ ࣥ 㓟 ᐁ ⬟ ᇶ ࢆ ᑟ ධ ࡋ ࡓ ࢚ ࢳ ࣞ ࣥ ࢢ ࣜ ࢥ ࣮ ࣝ ࣁ ࢻ ࣟ ࢤ ࣝ(PEG)ࡣ MSCsࡢ 㦵 ᙧ ᡂ ศ ⬟ ࢆ ಁ 㐍 ࡍ ࡿ ຠ ᯝ ࡀ ࠶ ࡗ ࡓ ࠋᐁ ⬟ ᇶ ௨ እ ࠊࢱ ࣥ ࣃ ࢡ ㉁ ࡢ ࡋ ࡚ ࠊ ࢱ ࣥ ࣃ ࢡ ㉁ ࡛ ࠶ ࡿ ࣇ ࣈ ࣟ ࢿ ࢡ ࢳ ࣥ(Fn)࡛ ಟ 㣭 ࡋ ࡓ ࢹ ࢪ ࢱ ࣭࣐ࣝ ࢡ ࣟ ࣑
ࣛ ࣮࣭ࢹ ࣂ ࢫ(DMD)ୖ ᇵ 㣴 ࡋ ࡓ MSCs ࡀ 㦵 ᙧ ᡂ ศ ⬟ ࢆ ಁ 㐍 ࡍ ࡿ ࡇ
ࢆ ㄆ ࡵ ࡽ ࢀ ࡓ[ 1 0 ]ࠋ ࡲ ࡓ ࠊ ⏕ య ᮦ ᩱ ୖ ␗ ࡞ ࡿ ᵓ 㐀 ࢆ ࡶ ࡘ ྠ ࡌ ࢱ ࣥ ࣃ ࢡ ㉁
࡛ ࡶ MSCs ࡢ 㦵 ᙧ ᡂ ศ ⬟ ᙳ 㡪 ࢆ ࠼ ࡿ ࡇ ࡀ ᫂ ࡽ ࡉ ࢀ ࡓ ࠋ Mauney[ 11 ]ࡽ ࡣ ࣛ ࢵ ࢺ ᑿ ࡼ ࡾ ᢳ ฟ ࡋ ࡓ 㓟 ྍ ⁐ ᛶ 㠀 ኚ ᛶ Ϩ ᆺ ࢥ ࣛ ࣮ ࢤ ࣥ ࡀ MSCs ࡢ 㦵 ᙧ ᡂ ศ ⬟ ࢆ ಁ 㐍 ࡋ ࡓ ୍ ᪉ ࠊኚ ᛶ Ϩ ᆺ ࢥ ࣛ ࣮ ࢤ ࣥ ࡀ MSCs ࡢ 㦵 ᙧ ᡂ ศ ⬟ ࢆ ಁ 㐍 ࡋ ࡞ ࠸ ⤖ ᯝ ࡞ ࡗ ࡓ ࠋ᭦ ࠊ⣽ ⬊ ᇵ 㣴 ─(TCPs)ࡼ ࡾ ࠊኚ ᛶ Ϩ ᆺ ࢥ ࣛ ࣮ ࢤ ࣥ ᇵ 㣴 ᇶ ᮦ ࡣ MSCs ࡢ 㦵 ᙧ ᡂ ศ ⬟ ࢆ ಁ 㐍 ࡋ ࡓ ࡇ ࢆ ሗ
࿌ ࡋ ࡓ[ 1 2 ]ࠋ ᭦ ࠊ ࢱ ࣥ ࣃ ࢡ ㉁ ࡣ ࣑ ࣀ 㓟 ࡛ ᵓ ᡂ ࡉ ࢀ ࡚ ࠸ ࡿ ࡀ ࠊ ࣑ ࣀ 㓟 㔜 ྜ య ࡢ ࣏ ࣜ ࣌ ࣉ ࢳ ࢻ ࡣ MSCs ࡢ 㦵 ᙧ ᡂ ศ ⬟ ࢆ ಁ 㐍 ࡍ ࡿ ຠ ᯝ ࡶ ࠶ ࡿ ࠋ Guo ࡽ ࡣ ࠊRGD[ 1 3 ]ࡸ 㦵 ᙧ ᡂ ࢱ ࣥ ࣃ ࢡ ㉁(BMP-2) [ 1 4 ]࡛ ಟ 㣭 ࡋ ࡓ PLGA ࡀ MSCs ࡢ 㦵 ⱆ ⣽ ⬊ ศ ⬟ ࢆ ಁ 㐍 ࡍ ࡿ ࡇ ࢆ ♧ ࡋ ࡓ ࠋChun[ 1 5 ]ࡽ ࡣ ࠊ ὀ ᑕ ᆺ ࡢ ឤ ⇕ ᛶ ࣏ ࣜ(࢜ ࣝ ࢞ ࣀ ࣍ ࢫ ࣇ ࢮ ࣥ)ࣄ ࢻ ࣟ ࢤ ࣝ ࢆ ࣛ ࢵ ࢺ ࡢ ⫼ ୰ ὀ ᑕ ࡋ ࠊRGD ࢆ ῧ ຍ ࡋ ࡓ ࣄ ࢻ ࣟ ࢤ ࣝ ࡀ MSCs ࡢ 㦵 ᙧ ᡂ ศ ⬟ ࢆ ಁ 㐍 ࡋ ࡓ ࡇ
ࢆ ሗ ࿌ ࡋ ࡓ ࠋMartino[ 1 6 ]ࡽ ࡣ ࠊࣇ ࣈ ࣟ ࢿ ࢡ ࢳ ࣥ(Fn)᩿ ∦ ࡣ ࣇ ࣈ ࣟ ࢿ ࢡ ࢳ ࣥ ࡼ ࡾ MSCs ࡢ 㦵 ᙧ ᡂ ศ ⬟ ࢆ ಁ 㐍 ࡛ ࡁ ࡿ ࡇ ࢆ ሗ ࿌ ࡋ ࡓ ࠋ
ࡉ ࡽ ࠊ⏕ య ᮦ ᩱ ࡢ ⾲ 㠃 ᙧ ែ ࡣ MSCs ࡢ ศ ᙳ 㡪 ࢆ ࠼ ࡿ ࡇ ࡀ ࢃ ࡗ ࡚ ࡁ ࡓ ࠋ
Olivares-Navarrete[ 1 ]ࡽ ࡣ ࠊࢳ ࢱ ࣥ ᯈ ࡢ ⢒ ࡉ ࢆ 0.8Ǎm ࡽ 3.22Ǎm ࡲ ࡛
ୖ ᪼ ࡋ ࠊMSCs ࡢ 㦵 ᙧ ᡂ ศ ⬟ ࢆ ಁ 㐍 ࡋ ࡓ ࠋBalloni[ 1 7 ]ࡽ ࡣ ࠊ 㔜 㓟 ࢚ ࢵ ࢳ ࣥ ࢢ ฎ ⌮ ࡋ ࡓ ࢳ ࢱ ࣥ ᯈ ୖ ᇵ 㣴 ࡋ ࡓ MSCs ࡣ 㦵 ᙧ ᡂ ࢱ ࣥ ࣃ ࢡ ㉁
2(BMP-2)ࠊRNA ࡽ 㦵 ⱆ ⣽ ⬊ ≉ ␗ ⓗ ㌿ ᅉ Ꮚ cbfa1ࠊOsx ࢆ Ⓨ ぢ ࡋ ࠊ Ϩ ᆺ ࢥ ࣛ ࣮ ࢤ ࣥ ࠊALP Ⓨ ぢ ࢆ ಁ 㐍 ࡋ ࠊ ┦ ᑐ ⓗ ࡞ ⢒ ࡉ ࡀ ࠶ ࡿ ⾲ 㠃 ࡀ MSCs ࡢ 㦵 ᙧ ᡂ ศ ⬟ ࢆ ಁ 㐍 ࡍ ࡿ ⤖ ᯝ ࢆ ㄆ ࡵ ࡓ ࠋRuckh[ 1 8 ]ࡽ ࡣ ࠊ⾲ 㠃 ࡀ ⢒ ࠸ ࣏ ࣜ dž-
࢝ ࣉ ࣟ ࣛ ࢡ ࢺ ࣥ(PCL) ࡢ ࢼ ࣀ ࣇ ࣂ ࣮ࡀ ࢫ ࣒ ࣮ ࢬ ࡞ PCL ࡼ ࡾ ࠊMSCs ࡢ ALP Ⓨ ぢ ࠊ ࢜ ࢫ ࢸ ࢜ ࣏ ࣥ ࢳ ࣥ ࠊ ࢜ ࢫ ࢸ ࢜ ࢝ ࣝ ࢩ ࣥ ࡢ 㧗 ⃰ ᗘ ࢆ ♧ ࡋ ࠊ 㦵
3 ᙧ ᡂ ศ ⬟ ࢆ ಁ 㐍 ࡉ ࢀ ࡚ ࠸ ࡿ ࡇ ࢆ ሗ ࿌ ࡋ ࡓ ࠋࡲ ࡓ ࠊ⬺ ⣽ ⬊ ࡉ ࢀ ࡓ ECM ᵓ 㐀(PCL/ECM)ࡣ PCLࡼ ࡾ MSCs ࡢ 㦵 ᙧ ᡂ ศ ⬟ ࢆ ಁ 㐍 ࡉ ࢀ ࡚ ࠸ ࡿ ࡇ
ࢆ ♧ ࡋ ࡓ[ 1 9 ]ࠋ ࣇ ࣂ ࣮ ⾲ 㠃 ࡢ ⢒ ࡉ ௨ እ ࠊ ࣇ ࣂ ࣮ ࡢ ┤ ᚄ ࡶ MSCs ࡢ 㦵 ᙧ ᡂ ศ ⬟ ࢆ ᙳ 㡪 ࡍ ࡿ ࠋTakahashi[ 2 0 ]ࡽ ࡣ ࠊࣇ ࣂ ࣮ ࡢ ┤ ᚄ ࠊ✵ 㝽 ⋡ ࡀ ␗ ࡞ ࡿ PET ⧊ ≀ ୖ MSCs ࢆ ᇵ 㣴 ࡋ ࠊ┤ ᚄ 9Ǎm ࣇ ࣂ ࣮ ࡘ ప ࠸ ✵ 㝽 ⋡ PET ᇵ 㣴 ᇶ ᮦ ୖ ࠾ ࡅ ࡿ MSCs ࡢ ALP Ⓨ ぢ ࠊ࢜ ࢫ ࢸ ࢜ ࢝ ࣝ ࢩ ࣥ ࡢ ⃰ ᗘ ࡀ 㧗 ࡃ ࠊ㦵 ᙧ ᡂ ศ ⬟ ࢆ ಁ 㐍 ࡍ ࡿ ຠ ᯝ ࡀ ࠶ ࡗ ࡓ ࡇ ࢆ ሗ ࿌ ࡋ ࡓ ࠋDing[ 2 1 ] ࢢ ࣝ ࣮ ࣉ ࡣ ␗ ࡞ ࡿ ࢧ ࢬ ࡢ ⣽ ⬊ ᥋ ╔ ࢆ 㜼 ᐖ ࡍ ࡿ PEG ཬ ࡧ ⣽ ⬊ ᥋ ╔ ࢆ ಁ 㐍 ࡍ ࡿ RGDࡢ ࣏ ࣜ ࣌ ࣉ ࢳ ࢻ ࢆ ⏝ ࡋ ࠊ ࣐ ࢡ ࣟ ࣃ ࢱ ࣮ ࣥ ࢽ ࣥ ࢢ ࡋ ࡓ ⏕ య ᮦ
ᩱ ⾲ 㠃 ୖ MSCs ࢆ ᇵ 㣴 ࡋ ࠊ⣽ ⬊ 㛫 ࡢ ┦ స ⏝ ࡼ ࡾ ⬡ ⫫ ⣽ ⬊ ཬ ࡧ 㦵 ⱆ ⣽
⬊ ࡢ ศ ࢆ ಁ 㐍 ࡉ ࢀ ࡚ ࠸ ࡿ ࡇ ࢆ ♧ ࡋ ࡓ ࠋDalby[ 2 2 ]ࡽ ࡣ ῝ ࡉ 120nmࠊ 㛫 㝸 200nm ࡢ ࣏ ࣜ ࣓ ࢱ ࢡ ࣜ ࣝ 㓟 ࣓ ࢳ ࣝ(PMMA)ୖ ᇵ 㣴 ࡋ ࡓ ࡇ ࢁ ࠊMSCs ࡣ ࡽ ࡞ PMMA ᮦ ᩱ ࡼ ࡾ 㦵 ᙧ ᡂ ศ ⬟ ࢆ ಁ 㐍 ࡋ ࡓ ࠋ ࡲ ࡓ ࠊ ࢳ ࢱ ࣥ ࢼ ࣀ ࢳ ࣗ ࣮ ࣈ ᒙ ࢆ ᣢ ࡘ ⏕ య ᮦ ᩱ ୖ MSCs ࢆ ᇵ 㣴 ࡍ ࡿ ࠊ ┤ ᚄ 100nm ࡢ ࢳ ࢱ
ࣥ ࢼ ࣀ ࢳ ࣗ ࣮ ࣈ ᒙ ୖ ࠾ ࡅ ࡿ MSCs ࡀ 㦵 ⱆ ⣽ ⬊ ࡢ ศ ࢆ ಁ 㐍 ࡋ ࠊ ┤ ᚄ 30nmࡢ ࢳ ࢱ ࣥ ࢼ ࣀ ࢳ ࣗ ࣮ ࣈ ᒙ ୖ ࡣ MSCsࡢ ቑ Ṫ ࡋ ࡛ ࡁ ࡞ ࠸ ⤖ ᯝ ࡀ ㄆ ࡵ
ࡽ ࢀ ࡓ[ 2 3 , 2 4 ]ࠋMarletta[ 2 5 ]ࡽ ࡣ 10keV He ࡛ ฎ ⌮ ࡋ ࡓ ࣑ ࢡ ࣟ ┦ ศ 㞳 ࡢ PCL ࡣ MSCs ࡢ 㧗 ࠸ 㦵 ᙧ ᡂ ศ ⬟ ࢆ ♧ ࡋ ࡓ ࠋ
ࡲ ࡓ ࠊᗄ ఱ Ꮫ ⓗ ᙧ ≧ ᑐ ࡍ ࡿ ⏕ య ᮦ ᩱ ࡣ MSCs ࡢ ศ ᙳ 㡪 ࢆ ࠼ ࡿ ࡇ
ࡀ ࢃ ࡗ ࡚ ࡁ ࡓ ࠋ
Ruiz[ 2 6 ]ࡽ ࡣ ࠊ ࣐ ࢡ ࣟ ༳ ๅ ᢏ ⾡ ࡛ ᙧ ⦤ ≧ ࣇ ࣈ ࣟ ࢿ ࢡ ࢳ ࣥ ࢆ ࢞ ࣛ ࢫ
⾲ 㠃 ୖ ࢥ ࣮ ࢸ ࣥ ࢢ ࡋ ࠊMSCs ࢆ ᇵ 㣴 ࡋ ࠊ 㦵 ཬ ࡧ ⬡ ⫫ ㄏ ᑟ ᇵ 㣴 ᾮ ࡛ ࠊ ᙧ ୰ ᚰ ࠸ ࡿ MSCs ࡀ ⬡ ⫫ ⣽ ⬊ ศ ࡋ ࠊ ୰ ᚰ ࡢ ࿘ ࡾ ࠸ ࡿ MSCs ࡀ 㦵 ⱆ ⣽ ⬊ ศ ࡋ ࡓ ࡀ ࠊ ᙧ ࡢ ┤ ᚄ 㛵 ಀ ࡞ ࠸ ⤖ ᯝ ࡞ ࡗ ࡓ ࠋ᭦ ࠊṇ ᪉ ᙧ ࠊ 㛗 ᪉ ᙧ ࠊᴃ ࠊ༙ ᴃ ᙧ ࡢ ⦤ ≧ ࡢ ෆ ഃ ࠾ ࡅ ࡿ MSCs ࡀ ⬡ ⫫ ⣽ ⬊ ศ ࡋ ࠊ እ ഃ ࠾ ࡅ ࡿ MSCs ࡀ 㦵 ⱆ ⣽ ⬊ ศ ࡍ ࡿ ࡇ ࢆ ♧ ࡋ ࡓ ࠋྠ ࡌ ࡼ ࠺ ࠊฝ 㠃 ࠾ ࡅ ࡿ MSCs ࡣ 㦵 ⱆ ⣽ ⬊ ศ ࡋ ࡸ ࡍ ࡃ ࠊ พ 㠃 ࠾ ࡅ ࡿ MSCs ࡣ ⬡
⫫ ⣽ ⬊ ศ ࡋ ࡸ ࡍ ࠸ ⤖ ᯝ ࡞ ࡗ ࡓ ࠋࡍ ࡞ ࢃ ࡕ ࠊฝ 㠃 ཷ ࡅ ࡿ ᛂ ຊ ࡣ พ 㠃
ཷ ࡅ ࡿ ᛂ ຊ ࡢ 3 ಸ ࠊ␗ ࡞ ࡿ ᛂ ຊ ࡛ ⣽ ⬊ 㦵 ᱁ ࢆ ᙳ 㡪 ࡋ ࡓ ཎ ᅉ ࡞ ࡾ ࠊMSCs ࡀ ␗ ࡞ ࡿ ศ ᪉ ྥ ࡞ ࡗ ࡓ ⪃ ࠼ ࡽ ࢀ ࡿ ࠋ
ࡲ ࡓ ࠊ⏕ య ᮦ ᩱ ࡢ ᙎ ᛶ ࡣ MSCs ࡢ ศ ᙳ 㡪 ࢆ ࠼ ࡿ ࡇ ࡶ ࢃ ࡗ ࡚ ࡁ ࡓ ࠋ
MSCs ࡣ ຊ Ꮫ ⓗ ࡞ ᙳ 㡪 ࢆ ཷ ࡅ ࡛ ࠊ ࡑ ࢀ ᚑ ࡗ ࡚ ࠊ ⏕ ≀ ᛂ ࢆ ⏕ ࡌ ࠊ ᖿ ⣽
⬊ ࡢ ศ ࡢ ᙳ 㡪 ࢆ ⏕ ࡌ ࡿ ࠋEngler[ 2 7 ]ࡽ ࡣ ␗ ࡞ ࡿ ᙎ ᛶ ࢆ ᣢ ࡘ ⭷ PAA㹫 ୖ ࡢ MSCs ࡢ 㦵 ᙧ ᡂ ศ ⬟ ࡢ ᙳ 㡪 ࢆ ㄪ ࡓ ⤖ ᯝ ࠊప ࠸ ᙉ ᗘ(0.1㸫 㸯Kpa)ࡢ ሙ
ྜ ࠊMSCs ࡀ ⚄ ⤒ ⣽ ⬊ ศ ࡋ ࠊᙉ ᗘ(8㸫17Kpa)ࡢ ሙ ྜ ࠊMSCs ࡀ ➽ ཎ ⣽
4
⬊ ศ ࡋ ࠊ ᙉ ࠸ ᙉ ᗘ(25㸫40Kpa)ࡢ ሙ ྜ ࠊMSCs ࡀ 㦵 ⱆ ⣽ ⬊ ศ ࡍ ࡿ ࡇ ࢆ ♧ ࡋ ࡓ ࠋ ᭦ ࠊ ࢥ ࣛ ࣮ ࢤ ࣥ ᮦ ᩱ ࡣ PET ࢆ ΰ ධ ࡍ ࡿ ࡇ ࡛ ࠊ ࢥ ࣛ ࣮ ࢤ ࣥ ࡢ ᙉ ᗘ ࢆ ୖ ᪼ ࡋ ࠊMSCs ࡢ 㦵 ᙧ ᡂ ศ ⬟ ࢆ ಁ 㐍 ࡍ ࡿ[ 2 8 ]ࠋFu[ 2 9 ]ࡽ ࡣ ࠊ
࣐ ࢡ ࣟ 㓄 ิ ࢚ ࣛ ࢫ ࢺ ࣐ ࣮ ᰕ ≧ ᇵ 㣴 ᇶ ᮦ ࢆ ⏝ ࡋ ࠊᚤ ᰕ ࡢ 㧗 ࡉ ࢆ ኚ ࡍ ࡿ ࡇ
࡛ ࠊ ᙎ ᛶ ࢆ ࢥ ࣥ ࢺ ࣟ ࣮ ࣝ ࡛ ࡁ ࠊMSCs ࢆ ᇵ 㣴 ࡋ ࡓ ⤖ ᯝ ࠊ 㧗 ࠸ ᙎ ᛶ ⋡(≌ ᘬ ຊ 30㹬N ௨ ୖ)ࢆ ᣢ ࡘ ᇶ ᮦ ୖ ࡛ MSCs ࡢ 㦵 ᙧ ᡂ ศ ⬟ ࡀ ಁ 㐍 ࡉ ࢀ ࡚ ࠸ ࡿ ࡇ ࢆ ♧ ࡋ ࡓ ࠋ⏕ య እ ᇵ 㣴 ࡛ ࡣ ࠊຊ Ꮫ ⓗ ࡞ ่ ⃭ ࢆ ཷ ࡅ ࡿ MSCs ࡣ ㎿ ㏿ ᛂ ࡋ ࠊ⣽ ⬊ ⾲ 㠃 ࡢ ཷ ᐜ య ࡸ ࠊ᥋ ╔ ࢧ ࢻ ࢆ ᙳ 㡪 ࡍ ࡿ ࠊ⣽ ⬊ ෆ ࡢ ࢩ ࢢ ࢼ ࣝ ಙ ྕ ࡢ ୍ 㐃 ⓗ ࡞ ᛂ ࢆ ㉳ ࡇ ࡾ ࠊ ≉ ␗ ⓗ ࡞ DNA ࡸ ࠊ ⣽ ⬊ እ ࢱ ࣥ ࣃ ࢡ ㉁ ࢆ ศ Ἢ ࡍ ࡿ[ 3 0 ]ࠋ ௨ ୖ ࡢ ࡇ ࡼ ࡗ ࡚ ࠊ ◳ ࠸ ᇵ 㣴 ᇶ ᮦ ୖ MSCs ࡀ 㦵 ⱆ ⣽ ⬊ ศ ࡋ ࠊ 㦵 ᙧ ᡂ ศ ⬟ ࢆ ಁ 㐍 ࡍ ࡿ ຠ ᯝ ࡀ ࠶ ࡿ ࠋ
௨ ୖ ࡼ ࡾ ࠊ ⏕ య ᮦ ᩱ ศ 㔝 ࠾ ࠸ ࡛ ࠊ ࡑ ࡢ ⾲ 㠃 ࡢ ᚤ ⣽ ࡞ ኚ ࡀ MSCs ࡢ ศ ᙳ 㡪 ࢆ ࠼ ࡿ ࡇ ࡣ ᫂ ࡽ ࡛ ࠶ ࡿ ࠋ
୍ ᪉ ࠊ⣽ ⬊ ⏕ ≀ Ꮫ ศ 㔝 ࠾ ࠸ ࡛ ࠊ⏕ య ᮦ ᩱ ⾲ 㠃 ࡢ ᛶ ≧ ࡣ ⣽ ⬊ ࡢ ᥋ ╔ 㸪ቑ Ṫ 㸪ศ ࡞ ࡢ ᇶ ᮏ ⓗ ࡞ ⣽ ⬊ ᣲ ື ࡁ ࡃ 㐃 ື ⓗ ᙳ 㡪 ࢆ ࠼ ࡿ ࡇ ࡶ ࢃ
ࡗ ࡚ ࡁ ࡓ ࠋࡑ ࡢ ᙳ 㡪 ࢆ ᫂ ࡽ ࡋ ࡓ ࡢ ࡣ ㌾ 㦵 ⣽ ⬊ ࡢ ᇵ 㣴 ◊ ✲ ࡛ ࠶ ࡿ ࠋ⣽
⬊ ࡢ ㊊ ሙ ⎔ ቃ ࡼ ࡾ ࠊ㌾ 㦵 ⣽ ⬊ ࡣ ⧄ ⥔ ⱆ ⣽ ⬊ ࡢ ┦ ㌿ ࡀ ࡛ ࡁ ࡿ ࠋࡘ ࡲ
ࡾ ࠊ⣽ ⬊ ࡀ ࠸ ᙧ ែ ࡞ ࡿ ሙ ྜ ࠊ≉ ᭷ ࡞ ϩ ᆺ ࢥ ࣛ ࣮ ࢤ ࣥ ࢆ ྜ ᡂ ࡍ ࡿ ࡇ ࡀ
࡛ ࡁ ࡿ ࠋ୍ ᪉ ࠊ㌾ 㦵 ⣽ ⬊ ࡀ ࠸ ᙧ ែ ࢆ ኻ ࠺ ሙ ྜ ࠊ⧄ ⥔ ⱆ ⣽ ⬊ ≉ ᚩ ⓗ ࡞ Ϩ ᆺ ࢥ ࣛ ࣮ ࢤ ࣥ ࢆ ྜ ᡂ ࡋ ጞ ࡲ ࡿ ࠋ ㄽ ࠊࡑ ࡢ ㏫ ㌿ ࡶ ྍ ⬟ ࡛ ࠶ ࡿ ࠋ⧄ ⥔ ⱆ ⣽
⬊ ᵝ ኚ ࡋ ࡓ ㌾ 㦵 ⣽ ⬊ ࢆ ᇵ 㣴 ─ ࡽ 㟼 ࡣ ࡀ ࡋ ࡚ ࢞ ࣟ ࣮ ࢫ ࡢ ᇵ 㣴
─ ⛣ ࡍ ࠊ ࢞ ࣟ ࣮ ࢫ ࡢ ࢤ ࣝ ࡀ ⣽ ⬊ ࡢ ࿘ ᅖ ࢆ ᅖ ࡴ ࡢ ࡛ ⣽ ⬊ ࡣ ᇶ ㉁ ᥋ ╔ ࡏ ࡎ Ᏹ ᾋ ࡁ ࠊ ࠸ ᙧ ࢆ ྲྀ ࡽ ࡊ ࡿ ࠾ ࠼ ࡞ ࡃ ࡞ ࡿ[ 3 1 ]ࠋ ࡇ ࡢ ࡼ ࠺ ࡞ ≧ ἣ ࡛ ࡣ ⣽ ⬊ ࡣ ㌾ 㦵 ⣽ ⬊ ࡢ ᛶ ㉁ ᡠ ࡾ ࠊ ࡧ ϩ ᆺ ࢥ ࣛ ࣮ ࢤ ࣥ ࢆ స ࡾ ጞ ࡲ ࡿ ࠋ ࡍ ࡞ ࢃ ࡕ ࠊ⏕ య ᮦ ᩱ ศ 㔝 ࠾ ࡅ ࡿ ⾲ 㠃 ᛶ ≧ ࡢ ᭱ 㐺 ࢆ ゎ ᫂ ࡍ ࡿ ࡓ ࡵ ࠊࡑ ࡢ ᮦ ᩱ ୖ ࠾ ࡅ ࡿ ⣽ ⬊ ࡢ ึ ᮇ ᥋ ╔ ᙧ ែ ࡀ 㔜 せ ࡞ ᙺ ࢆ ᢸ ࠺ ࡇ ࢆ ⪃ ࠼ ࡽ
ࢀ ࡿ ࠋ
௨ ๓ ࠊᡃ ࠎ ◊ ✲ ࢢ ࣝ ࣮ ࣉ ࡣ ࠊ ࣃ ࢱ ࢺ ࢥ ࣮ ࢸ ࣥ ࢢ ࡋ ࡓ ࢩ ࣝ ࢡ ⧄ ⥔ ୖ
࠾ ࡅ ࡿ 㛫 ⴥ ⣔ ᖿ ⣽ ⬊(MSCs)ࡢ ࠸ ᙧ ែ ཬ ࡧ ࢩ ࣝ ࢡ ⧄ ⥔ ୖ ࠾ ࡅ ࡿ MSCs ࡢ ⣳ 㗽 ᙧ ែ ࢆ ほ ᐹ ࡋ ࠊᇵ 㣴 3 㐌 㛫 ᚋ ࡢ 㦵 ᙧ ᡂ ศ ⬟ ࡀ ␗ ࡞ ࡿ ⤖ ᯝ ࢆ ㄆ ࡵ ࡓ[ 3 3 ]ࠋ
5 ᅗ 1.1. 㛫 ⴥ ⣔ ᖿ ⣽ ⬊(MSCs)ࡢ ࠸ ᥋ ╔ ᙧ ែ ཬ ࡧ 㦵 ᙧ ᡂ ศ ⬟[ 3 3 ] ࡋ ࡋ ࡞ ࡀ ࡽ ࠊ ձSEM ⏬ ീ ࡛ ࡣ ≉ ᚩ ࡀ ࠶ ࡿ ⣽ ⬊ ࡋ ྲྀ ࢀ ࡎ ࠊ ୍ ⯡ ࡉ
ࢀ ࡚ ࠸ ࡞ ࠸ Ḟ Ⅼ ࡀ ࠶ ࡿ ࠋࡲ ࡓ ࠊղ ⣽ ⬊ ึ ᮇ ᥋ ╔ ᙧ ែ ࡣ ࠸ ᙧ ែ ཬ ࡧ ⣳ 㗽 ᙧ
ែ ࡀ ほ ᐹ ࡛ ࡁ ࡓ ࡶ ࡢ ࡢ ࠊᩘ Ꮠ ࡉ ࢀ ࡚ ࠾ ࡽ ࡎ ࠊ◊ ✲ ࡢ ࣥ ࣃ ࢡ ࢺ ࡀ ᙅ ࠸ Ḟ Ⅼ ࡶ ࠶ ࡿ ࠋ
⣽ ⬊ ᙧ ែ ࡢ ほ ᐹ ᪉ ἲ ཬ ࡧ ᩘ Ꮠ ࡢ ◊ ✲ ࡘ ࠸ ࡚ ࠊᡃ ࠎ ࡣ ⣽ ⬊ ࡢ ⏬ ീ ᢏ
⾡ ࢆ 㛤 Ⓨ ࡋ ࡓ ࠋ(⠇ 1.3.3)
ࡲ ࡓ ࠊ⏕ య ᮦ ᩱ ࡢ ⾲ 㠃 ᛶ ≧ ࠊ⣽ ⬊ ࡢ ึ ᮇ ᥋ ╔ ᙧ ែ ཬ ࡧ ⣽ ⬊ ศ ࡢ ࣓ ࢝ ࢽ ࢬ ࣒ ࡋ ࡚ ࠊࠕ ⣽ ⬊ ࡽ ᮦ ᩱ ⬟ ື ⓗ ࢩ ࢢ ࢼ ࣝ ࡀ ㏦ ࡽ ࢀ ࡚ ࠸ ࡿ ࠖ ࡢ ࡣ 㛫 㐪
࠸ ࡞ ࠸ ⪃ ࠼ ࡽ ࢀ ࡚ ࠸ ࡿ ࠋ ࠼ ࡤ ࠊ⣽ ⬊ ࡀ ᮦ ᩱ ࢆ ⁐ ゎ ࡋ ࠊࡑ ࡢ ⤖ ᯝ ࠊ㐟 㞳 ࡋ ࡓ Ꮫ ≀ ㉁ ࡀ ࢩ ࢢ ࢼ ࣝ ࡞ ࡗ ࡚ ࠸ ࡿ ࡶ ⪃ ࠼ ࡽ ࢀ ࡿ ࠋࡶ ࡋ ࡑ ࠺ ࡛ ࡞ ࡅ ࢀ ࡤ ࠊ⣽ ⬊ ࡣ ࠊࡇ ࢀ ࡲ ࡛ ⪃ ࠼ ࡽ ࢀ ࡚ ࠸ ࡓ ࡼ ࡾ ࡣ ࡿ 㧗 ᗘ ࡞ ㄆ ㆑ ࢩ ࢫ ࢸ ࣒ ࢆ
ࡶ ࡗ ࡚ ࠸ ࡿ ࡇ ࡞ ࡿ[ 3 4 ]ࠋ ࠼ ࡤ ࠊᅗ 1.2 ࡛ ♧ ࡋ ࡓ ㏻ ࡾ ࠊ⣽ ⬊ ࡣ ࣥ ࢸ ࢢ
ࣜ ࣥ ࡸ ࢱ ࣥ ࣃ ࢡ ㉁ ࢆ ࡋ ࡚ ⏕ య ᮦ ᩱ ᥋ ╔ ࡍ ࡿ ࡀ ࠊ⣽ ⬊ ࡀ ᮦ ᩱ ࢆ ⁐ ゎ ࡍ ࡿ ࡇ ࡛ ࠊ ⣽ ⬊ እ ࡢ ᚤ ᑠ ✵ 㛫 ࡶ ⁐ ゎ ࡉ ࢀ ࡓ ≀ ㉁(⏕ య ᮦ ᩱ ࡢ ᚤ 㔞 Ꮚ ࡸ ࠊ
࢜ ࣥ ࡞ )ࢆ Ꮡ ᅾ ࡍ ࡿ ࠋ ᚑ ࡗ ࡚ ࠊ ␗ ࡞ ࡿ ⏕ య ᮦ ᩱ ୖ ࠾ ࡅ ࡿ ⣽ ⬊ ࡢ ึ ᮇ ᥋
╔ ᙧ ែ ࡀ ኚ 㔜 せ ࡞ ࡗ ࡚ ࡃ ࡿ ࠋ
6
ᅗ 1.2. ⏕ య ᮦ ᩱ ࡢ ⣽ ⬊ ᥋ ╔ 㐣 ⛬ ᥋ ╔ 㒊 ࡢ ᶍ ᘧ ᅗ[ 3 5 ]
⏕ య ᮦ ᩱ ࡢ ⾲ 㠃 ᛶ ≧ ࠾ ࡅ ࡿ ⣽ ⬊ ࡢ ึ ᮇ ᥋ ╔ ᙧ ែ ཬ ࡧ ศ ⬟ ࡢ ┦ 㛵 㛵 ࡍ ࡿ ◊ ✲ ࡣ ⏕ య ᮦ ᩱ ศ 㔝 ࡔ ࡅ ࡛ ࡣ ࡞ ࡃ ࠊ ⏕ ་ ⒪ ศ 㔝 ࡶ Ἴ ⣠ ࢆ ࡶ ࡓ ࡽ ࡍ ᮇ ᚅ ࡉ ࢀ ࡿ ࠋ
ᐇ ࡋ ࡚ ࠊே ࡢ 㦵 㧊 ࡽ ᥇ ྲྀ ࡋ ࡓ 㛫 ⴥ ⣔ ᖿ ⣽ ⬊ ࡢ ᇵ 㣴 ᢏ ⾡ ࢆ ᛂ ⏝ ࡋ ࠊ
⏘ ⥲ ◊ ࡛ ࡣ ⣙ 80 ࡢ ᝈ ⪅ ⏤ ᮶ ࡢ 㛫 ⴥ ⣔ ᖿ ⣽ ⬊ ࡢ ᇵ 㣴 ࢆ ே ᕤ 㛵 ⠇ ࡞ ࡢ ⏕ య ᮦ ᩱ ୖ ࡛ ⾜ ࡗ ࡚ ࡁ ࡓ ࡇ ࡛ ⏕ ᇵ 㣴 㦵 ࡢ స 〇 ࡀ ᐇ ⌧ ࡋ ࠊ㦵 ⏕ ་ ⒪ ࡢ ᗎ ᖥ ࢆ 㛤 ࠸ ࡓ ࠋ ࡋ ࡋ ࡞ ࡀ ࡽ ࠊ ᝈ ⪅ ⏤ ᮶ ࡢ ⣽ ⬊ ࡣ ྠ ୍ ⤌ ⧊ ⏤ ᮶ ࡛ ࠶ ࡗ ࡚ ࡶ ࠊ
ே ᕤ 㛵 ⠇ ࡞ ࡢ ⏕ య ᮦ ᩱ ୖ ࡛ ࡢ ⣽ ⬊ ศ ࡀ ࡁ ࡃ ␗ ࡞ ࡿ ࡇ ࡀ ☜ ㄆ ࡉ ࢀ
࡚ ⏕ ᇵ 㣴 㦵 ࡀ ᙧ ᡂ ࡛ ࡁ ࡎ ࠊᝈ ⪅ ࡢ ⛣ ᳜ ⒪ ࡀ ฟ ᮶ ࡞ ࠸ ࢣ ࣮ ࢫ ࡶ ሗ ࿌ ࡉ
ࢀ ࡚ ࠸ ࡿ ࠋᚑ ࡗ ࡚ ࠊ㦵 ⏕ ་ ⒪ ࡢ ᐇ ⏝ ࡢ ಁ 㐍 ࡣ ࠊ⛣ ᳜ ᮇ ᚅ ࡉ ࢀ ࡿ 㦵 ᙧ ᡂ ⬟ ࢆ ᭷ ࡋ ࡚ ࠸ ࡿ ࡇ ࢆ ࠊᇵ 㣴 ᪩ ᮇ ࡢ ⣽ ⬊ ᙧ ែ ࡼ ࡗ ࡚ ホ ౯ุ࣭ ᐃ ࡍ
ࡿ ᢏ ⾡ ࡢ ☜ ❧ ࡀ ồ ࡵ ࡽ ࢀ ࡚ ࠸ ࡿ ࡢ ࡀ ⌧ ≧ ࡛ ࠶ ࡿ ࠋ
ࡑ ࡇ ࡛ ᮏ ◊ ✲ ࡛ ࡣ ࠊୖ グ ㄢ 㢟 ࡢ ゎ Ỵ ࢆ ┠ ᣦ ࡋ ࡚ ࠊ㦵 ⏕ ་ ⒪ ⏝ ࠸ ࡿ ⏕ య ᮦ ᩱ ୖ ࠾ ࡅ ࡿ ᖿ ⣽ ⬊ ࡢ ศ ⬟ ຊ ࢆ ᪩ ᮇ ண ࡍ ࡿ ࡓ ࡵ ࡢ ホ ౯ ᢏ ⾡ 㛤
Ⓨ ㈨ ࡍ ࡿ ᇶ ♏ ⓗ ◊ ✲ ࢆ ࠾ ࡇ ࡞ ࡗ ࡓ ࠋල య ⓗ ࡣ ࠊᮏ ◊ ✲ ࡣ 㸪⁐ ゎ ᛶ ࡀ ␗
࡞ ࡿ 㦵 ⏕ ་ ⒪ ࡛ ỗ ⏝ ⏝ ࠸ ࡽ ࢀ ࡿ ࢭ ࣛ ࣑ ࢵ ࢡ ࢫ ⣔࣭㔠 ᒓ ⣔ ⏕ య ᮦ ᩱ ࡋ
࡚ ⏝ ࠸ ࡽ ࢀ ࡚ ࠸ ࡿ 㸪(1) 㠀 ྾ ᛶ ȕ-TCP ྵ ᭷ ࣃ ࢱ ࢺ ࢹ ࢫ ࢡ(➨ 3 ❶)㸪(2) ␗ ࡞ ࡿ ᚤ ⣽ ᵓ 㐀 ࢆ ᭷ ࡍ ࡿ ࣃ ࢱ ࢺ ࢹ ࢫ ࢡ(➨ 4 ❶)㸪(3) ✀ ࠎ ࡢ ࣃ ࢱ ࢺ ᒙ ࡛ ⾲ 㠃 ಟ 㣭 ࡋ ࡓ ࢳ ࢱ ࣥ ୖ(➨ 5 ❶)㸪 ࡢ 3 ✀ 㢮 ࢆ 㑅 ᢥ ࡋ 㸪 ࡇ
ࢀ ࡽ ⏕ య ᮦ ᩱ ࡢ ᭱ 㐺 ࡞ ⾲ 㠃 ᛶ ≧ ࢆ ᳨ ウ ࡋ ࠊ␗ ࡞ ࡿ ⏕ య ᮦ ᩱ ୖ ࠾ ࡅ ࡿ 㛫 ⴥ
7
⣔ ᖿ ⣽ ⬊ ࡢ ᇵ 㣴 ࡢ ᴟ ࡵ ࡚ ᪩ ᮇ ࠾ ࡅ ࡿ ⣽ ⬊ ᥋ ╔ 㠃 ✚ 㦵 ศ ࡢ ┦ 㛵 ࠊࡘ
ࡲ ࡾ ࠊ⣽ ⬊ ᣲ ື ࡢ ண ᢏ ⾡ ࡢ ᵓ ⠏ ࢆ ┠ ⓗ ࡋ ࡚ ࡶ ࡢ ࡛ ࠶ ࡿ ࠋࡲ ࡓ ࠊࢳ ࢱ ࣥ
ྜ 㔠 ୖ ಟ 㣭 ࡍ ࡿ ࣃ ࢱ ࢺ ᒙ ࡢ ᙧ ᡂ ᪉ ἲ ࡢ 㛤 Ⓨ ࡶ ┠ ⓗ ࡛ ࠶ ࡿ(➨ 2 ❶)ࠋ
᳨ ウ ࡋ ࡓ ᡂ ᯝ ࡋ ࡚ ࠊ ḟ ࡢ 2 Ⅼ ࡀ ᣲ ࡆ ࡽ ࢀ ࡿ ࠋ
ձ ึ ᮇ ᥋ ╔ 㠃 ✚ 㦵 ศ ⬟ ࡢ 㛫 ᙉ ࠸ ┦ 㛵 ᛶ ࡀ ࠶ ࡿ ࡇ ࢆ ぢ ฟ ࡋ ࡓ ࠋ (BBRC 430, 156-160 (2013))
ղ ᚤ ⣽ ᵓ 㐀 ࡢ ␗ ࡞ ࡿ ࣃ ࢱ ࢺ ᒙ ࢆ ⾲ 㠃 ᭷ ࡍ ࡿ ᇵ 㣴 ᇶ ᮦ ୖ ࡛ ࠊ㛫 ⴥ ⣔ ᖿ ⣽ ⬊ ࡢ ᥋ ╔ 㠃 ✚ ࡀ ᴟ ࡵ ࡚ ᪩ ᮇ㸦 ᇵ 㣴 㛤 ጞ 2 㛫 ᚋ 㸧 ␗ ࡞ ࡿ ࡇ ࢆ ぢ ฟ ࡋ ࡓ ࠋ(STAM 13, 209-214 (2012))
௨ ୖ ࡼ ࡾ ࠊ⏕ య ᮦ ᩱ ୖ ࠾ ࡅ ࡿ ⣽ ⬊ ࡢ ᇵ 㣴 ึ ᮇ ࡢ ᥋ ╔ 㠃 ✚ ࡽ ࠊศ ࢆ
᪩ ᮇ ண ࡛ ࡁ ࡿ ྍ ⬟ ᛶ ࡀ ᙉ ࡃ ♧ ၀ ࡉ ࢀ ࡓ ࠋ
1.2 ࡞ ᮦ ᩱ ศ ᯒ ᪉ ἲ 1.2.1 ㉮ ᰝ 㟁 Ꮚ 㢧 ᚤ 㙾
ձ 㠀 ྾ ᛶ ǃ-TCP ྵ ᭷ ࣃ ࢱ ࢺ ࢹ ࢫ ࢡ 㸪 ղ ␗ ࡞ ࡿ ᚤ ⣽ ᵓ 㐀 ࢆ ᭷ ࡍ ࡿ ࣃ ࢱ ࢺ ࢹ ࢫ ࢡ 㸪ճ ✀ ࠎ ࡢ ࣃ ࢱ ࢺ ᒙ ࡛ ⾲ 㠃 ಟ 㣭 ࡋ ࡓ ࢳ ࢱ
ࣥ ྜ 㔠 ୖ Ti Წ ࡢ ᯒ ฟ ≀ ࡢ ほ ᐹ ࡣ ࠊ ㉮ ᰝ 㟁 Ꮚ 㢧 ᚤ 㙾(XL30ࠊFEI Company Japan Ltd., Japan)ࢆ ⏝ ࡋ ࡓ ࠋ ࡲ ࡓ ࠊ ༳ ྍ 㟁 ᅽ ࡣ 5.00kv
タ ᐃ ࡋ ࡓ ࠋ ┿ ✵ ᗘ ࡀ 3.5×10㸫5Pa ௨ ୗ ࡢ ⎔ ቃ ࡛ ほ ᐹ ࢆ ⾜ ࡗ ࡓ ࠋ ࡓ ࡔ ࡋ ࠊ ほ ᐹ ࢆ ⾜ ࠺ ๓ ࠊ ࡍ ࡚ ࡢ ヨ ᩱ ࢆ 㔠 ╔ ࡋ ࡓ ࠋ
1.2.2 ⷧ ⭷ X ⥺ ᅇ ᢡ
ᮦ ᩱ ࡢ ⾲ 㠃 ࢆ ᵓ ᡂ ࡍ ࡿ ┦ ࡢ ྠ ᐃ ࢆ ⾜ ࠺
ࡓ ࡵ ࠊ(ᰴ)ࣜ ࢞ ࢡ 〇 ⷧ ⭷ X ⥺ ᅇ ᢡ ⨨ RINT-2250 ࢆ ⏝ ࠸ ࡓ ࠋ
⾲ 1.1. ࢭ ࣛ ࣑ ࢵ ࢡ ࢫ ⣔ ᮦ ᩱ ࡢ ⷧ ⭷ X ⥺ ᅇ ᢡ ᐃ ᮲ ௳
Mode Continuous scan
Target Monochromatized Cu Kǂ
Voltage 40 kV
Current 300 mA
lj Fixed-Angle 1.0000
Sampling step 0.02°(2lj㸧 Scanning speed 2.000 °/min
Slit system DS 0.20mm-RS 㛤 ᨺɆSS 㛤 ᨺ Scanning angle 2-60°㸦2lj㸧
8
⾲ 1.2. ࢳ ࢱ ࣥ 㔠 ᒓ ᮦ ᩱ ࡢ ⷧ ⭷ X ⥺ ᅇ ᢡ ᐃ ᮲ ௳
Mode Continuous scan
Target Monochromatized Cu Kǂ
Voltage 40 kV
Current 300 mA
lj Fixed-Angle 2.0000
Sampling step 0.02°(2lj㸧 Scanning speed 2.000 °/min
Slit system DS 0.20mm-RS 㛤 ᨺɆSS 㛤 ᨺ Scanning angle 2-60°㸦2lj㸧
1.3 ⣽ ⬊
⏕ ≀ ࡢ ᇶ ᮏ ⓗ ࡞ ༢ ࡛ ࠶ ࡾ ࠊ⣽ ⬊ ࡢ ᇶ ᮏ ᶵ ⬟ ࡢ ⤌ ࡳ ࡣ ࡍ ࡚ ࡢ ⏕ ≀ ࡛ ඹ ㏻ ࡛ ࠶ ࡿ ࠋࡲ ࡓ ࠊ⏕ ≀ ࡢ ಶ య ࡣ 1 ಶ ࡢ ⣽ ⬊ ࡽ ጞ ࡲ ࡾ ࠊࡑ ࡢ ศ ࡼ ࡗ
࡚ ᵓ ⠏ ࡉ ࢀ ࡿ ࠋࡘ ࡲ ࡾ ࠊࡑ ࡢ 1 ಶ ࡢ ⣽ ⬊ ࡣ ✀ ࢆ Ỵ ࡵ ࡿ 㑇 ఏ ሗ ࢆ 㐠 ࡪ ࡾ
≀ ࠸ ࠼ ࡿ ࠋ ࡍ ࡞ ࢃ ࡕ ⣽ ⬊ ࡣ ࿘ ᅖ ࡽ 㞟 ࡵ ࡓ ᮦ ᩱ ࢆ ⏝ ࠸ ࡚ ࠊ ྠ ࡌ ጼ ࢆ ࡋ ࠊ 㑇 ఏ ሗ ࢆ Ⅼ ࡍ ࡿ ᪂ ࡋ ࠸ ⣽ ⬊ ࢆ స ࡿ ࡋ ࡃ ࡳ ࢆ ࡶ ࡘ ࠋࡇ ࡢ ⬟ ຊ ࢆ ഛ ࠼ ࠺ ࡿ ࡶ ࡢ ࡣ ⣽ ⬊ ௨ እ ࡞ ࠸[ 3 1 ]ࠋ
1.3.1 㛫 ⴥ ⣔ ᖿ ⣽ ⬊(mesenchymal stem cell)
㛫 ⴥ ⣔ ᖿ ⣽ ⬊ ࡢ ู ྡ ࡣ 㛫 ⧊ ᖿ ⣽ ⬊ ࡛ ࠶ ࡿ ࠋMSCs ࡣ ࢫ ࢺ ࣟ ࣮ ࣐ ⣽ ⬊ ࡛
࠶ ࡾ ࠊ⮬ ᕫ ⏕ ࡍ ࡿ ከ ⬟ ᛶ ࢆ ᣢ ࡘ ࠋࡲ ࡓ ࠊ㦵 㧊 ࡢ ࢫ ࢺ ࣟ ࣮ ࣐ ⣽ ⬊ ࡣ ⤖ ྜ ⤌
⧊ ࡢ ⼥ ㏻ ᛶ ࢆ ♧ ࡍ ዲ ࡛ ࠶ ࡿ ࠋࡑ ࡢ ⣽ ⬊ ࡣ ⧄ ⥔ ⱆ ⣽ ⬊ ࡢ ୍ ✀ ⪃ ࠼ ࡿ ሙ ྜ
ࡶ ࠶ ࡾ ࠊ㦵 㧊 ࡽ ྲྀ ࡾ ฟ ࡋ ࡚ ᇵ 㣴 ࡛ ࡁ ࡿ ࡢ ࡛ ࠊ୍ ಶ ࡢ ࢫ ࢺ ࣟ ࣮ ࣐ ⣽ ⬊ ࢆ ♽ ඛ ࡍ ࡿ Ꮚ Ꮮ ⣽ ⬊ ࡢ 㔞 ࢡ ࣟ ࣮ ࣥ ࢆ ධ ᡭ ࡛ ࡁ ࡿ ࠋᇵ ᆅ ࢩ ࢢ ࢼ ࣝ ࢱ ࣥ ࣃ ࢡ
ࢆ ຍ ࠼ ࡿ ࠊቑ Ṫ ࢆ ⥆ ࡅ ࡉ ࡏ ࡚ ྠ ᆺ ࡢ ⣽ ⬊ ࢆ స ࡾ ฟ ࡋ ࡓ ࡾ ࠊ⬡ ⫫ ⣽ ⬊ ࡸ ㌾ 㦵 ⣽ ⬊ ࡸ 㦵 ⣽ ⬊ ศ ࡉ ࡏ ࡓ ࡾ ࡛ ࡁ ࡿ[ 3 1 ]ࠋࡲ ࡓ ࠊMSCs ࡣ ᢠ ⅖ ⬟ ຊ ࡀ ࠶
ࡾ ࠊ య ෆ ⛣ ᳜ ࡋ ࡓ ᚋ ࠊ ⅖ ᛂ ࢆ ㉳ ࡇ ࡍ ⎔ ቃ ࡛ ࡶ ⏕ Ꮡ ࡛ ࡁ ࡿ ࠋ
9 ᅗ 1.3. 㛫 ⴥ ⣔ ᖿ ⣽ ⬊(MSC)ࡢ 㦵 ⱆ ⣽ ⬊ ࡢ ศ 㦵 ᙧ ᡂ[ 3 2 ]
⣽ ⬊ 㛵 ࡍ ࡿ ◊ ✲ ࡛ ࡣ ࠊ ࢱ ࣥ ࣃ ࢡ ㉁ ࠊDNAࠊRNA ࡞ ࡢ ศ ᯒ ᡭ ἲ ࢆ
⏝ ࠸ ࡓ ࡶ ࡢ ࠊ㢧 ᚤ 㙾 ࢆ ⏝ ࠸ ࡿ ⣽ ⬊ ᣲ ື ࡢ ほ ᐹ ᪉ ἲ ࢆ ࡶ ࡕ ࠸ ࡓ ࡶ ࡢ ࡢ ㏻ ࡾ ࡀ ὶ ࡛ ࠶ ࡿ ࠋ
1.3.2 ࡞ ⣽ ⬊ ほ ᐹ ᪉ ἲ
⣽ ⬊ ࡢ ᣲ ື ࢆ ▱ ࡿ ୖ ࡛ ࠊ ࡑ ࡢ ᥋ ╔ ᙧ ែ ࢆ ▱ ࡿ ࡇ ࡣ ྍ Ḟ ࡛ ࠶ ࡿ ࠋ19 ୡ ⣖ ࡢ ึ 㢌 ࠊ ඃ ࢀ ࡓ ග Ꮫ 㢧 ᚤ 㙾 ࡀ ⌧ ࢀ ࡚ ࡽ ࠊ1838 ᖺ Schleiden Schwannࡀ ⣽ ⬊ ㄝ(cell doctrine)ࢆ ᥦ ㉳ ࡋ ࠊ⣽ ⬊ ⏕ ≀ Ꮫ ࡀ ㄌ ⏕ ࡋ ࡓ ࠋࡲ ࡓ ࠊ ග Ꮫ 㢧 ᚤ 㙾 ࠺ ྍ ど ග ࡣ ࠊᑐ ㇟ ࢆ ◚ ቯ ࡋ ࡃ ࠸ ࠸ ࠺ Ⅼ ࡀ ࠶ ࡿ ࠋ≉
ᐃ ࡢ ⣽ ⬊ ᡂ ศ ⺯ ග ࢱ ࣥ ࣃ ࢡ ࡞ ࡢ ⺯ ග ᶆ ㆑ ࢆ ࡘ ࡅ ࠊ⏕ ⣽ ⬊ ෆ ࡛ ࡢ 㐠 ື ࡸ
┦ స ⏝ ࢆ ࡑ ࡢ ࡲ ࡲ ほ ᐹ ࡛ ࡁ ࡿ ࠋࡋ ࡋ ࠊග Ꮫ 㢧 ᚤ 㙾 ࡣ ྍ ど ග ࡢ Ἴ 㛗
ࡼ ࡿ ศ ゎ ⬟ ࡢ 㝈 ⏺ ࡀ ࠶ ࡿ[ 3 1 ]ࠋ
1.3.3 ⣽ ⬊ ึ ᮇ ᥋ ╔ ᙧ ែ ࡢ ⏬ ീ ᢏ ⾡
⣽ ⬊ ࢆ LIVE/DEAD ヨ ⸆ ࡛ 1 㛫 ᰁ Ⰽ ࡍ ࡿ[ 3 3 , 3 6 ]
ⴠ ᑕ ᆺ ⺯ ග 㢧 ᚤ 㙾 ࡛ ほ ᐹ ࡋ ࠊ ⏬ ീ ࡍ ࡿ
⏬ ീ ฎ ⌮ ᑓ ⏝ ࡢ ᕷ ㈍ ࢯ ࣇ ࢺ ࡛ ⣽ ⬊ ึ ᮇ ᥋ ╔ 㠃 ✚ ࢆ ゎ ᯒ ࡍ ࡿ
ᮏ ◊ ✲ ࡛ ࡣ ࠊ ⣽ ⬊ ึ ᮇ ᥋ ╔ 㠃 ✚ ࢆ ☜ ㄆ ࡍ ࡿ ࡓ ࡵ ࠊ ⣽ ⬊ ᰁ Ⰽ ᾮ ࡋ ࡚ LIVE/DEADヨ ⸆ ࢆ ⏝ ࡋ ࡓ ࠋLIVE/DEAD ヨ ⸆ ࡣ ࢝ ࣝ ࢭ ࣥ AM(⏕ ⣽ ⬊ ᰁ Ⰽ ࠊ ⥳ Ⰽ ⣲)ཬ ࡧ ࢚ ࢳ ࢪ ࢘ ࣒ ࣍ ࣔ ࢲ ࣐ ࣮1(Ṛ ⣽ ⬊ ᰁ Ⰽ ࠊ ㉥ Ⰽ ᰁ Ⰽ) ࡀ ྵ ࡲ ࢀ ࡚ ࠸ ࡿ ࠋ ⏕ ⣽ ⬊ ࡢ ሙ ྜ ࠊ ⣽ ⬊ ⭷ ㏱ 㐣 ᛶ ࢆ ᣢ ࡘ ࢝ ࣝ ࢭ ࣥ AM ࡣ ࠊ
⣽ ⬊ ෆ ࡢ ࢚ ࢫ ࢸ ࣛ ࣮ ࢮ ࡼ ࡿ ຍ Ỉ ศ ゎ ࡛ ⺯ ග ࢆ ♧ ࡍ ࢝ ࣝ ࢭ ࣥ ࡞ ࡿ ࠋࡲ
㛫ⴥ⣔
ᖿ⣽⬊
๓㦵ⱆ
⣽⬊
㦵ⱆ
⣽⬊
᪂⏕㦵 ᙧᡂ
ALPⓎぢ
࢜ࢫࢸ࢜࢝ࣝࢩࣥⓎぢ
▼⅊(㦵ᇶ㉁ᙧᡂ)
㦵ᇶ㉁
10
ࡓ ࠊ ࢝ ࣝ ࢭ ࣥ ࡣ ࢇ ⣽ ⬊ ẘ ᛶ ࢆ ᣢ ࡓ ࡎ ࠊ ⭷ ㏱ 㐣 ᛶ(⣽ ⬊ ⭷ ࡽ ࡢ
₃ ฟ ࡀ ࡞ ࠸)ࡢ ྜ ≀ ࡛ ࠊ Ἴ 㛗 530nm ㏆ ࡢ ࠊ ᙉ ࠸ 㯤 ⥳ Ⰽ ࡢ ⺯ ග ࢆ ♧ ࡍ ࠋ
୍ ᪉ ࠊ Ṛ ⣽ ⬊ ࡢ ሙ ྜ ࠊ ࢚ ࢳ ࢪ ࢘ ࣒ ࣍ ࣔ ࢲ ࣐ ࣮1 ࡣ ⣽ ⬊ ⭷ ᵓ 㐀 ࡢ ኚ క
࠸ ⣽ ⬊ ⭷ ࢆ ㏱ 㐣 ࡋ ࠊ ⣽ ⬊ ᰾ ࡢ DNA ⤖ ྜ ࡋ ࠊ Ἴ 㛗 585nm ㏆ ࡛ ㉥ Ⰽ ࡢ
⺯ ග ࢆ Ⓨ ࡍ ࡿ ࠋ
ࡇ ࢀ ࡲ ࡛ ࠊ ᡃ ࠎ ࡢ ◊ ✲ ࢢ ࣝ ࣮ ࣉ ࡛ ࡣ ࠊ ࢳ ࢱ ࣥ 㔠 ᒓ ᮦ ᩱ ୖ ࡛ ࡢ LIVE/DEAD ヨ ⸆ ࡛ ᰁ Ⰽ ࡋ ࡓ 㛫 ⴥ ⣔ ᖿ ⣽ ⬊ ࡢ ᥋ ╔ ᙧ ែ ࢆ ほ ᐹ ࡋ ࡓ ⤖ ᯝ ࠊᚓ
ࡽ ࢀ ࡓ ▱ ぢ ࢆ ሗ ࿌ ࡋ ࡓ[ 3 4 ]ࠋ ࡲ ࡓ ࠊ ྠ ࡌ ⣽ ⬊ ほ ᐹ ᡭ ἲ ࢆ ⏝ ࡋ ࡚ ࠊ ࣃ ࢱ
ࢺ ࢥ ࣮ ࢸ ࣥ ࢢ ࡋ ࡓ ࢩ ࣝ ࢡ ᮦ ᩱ ཬ ࡧ ࣃ ࢱ ࢺ ࢥ ࣮ ࢸ ࣥ ࢢ ࡋ ࡞ ࠸ ࢩ
ࣝ ࢡ ᮦ ᩱ ୖ ࡛ ࡢ 㛫 ⴥ ⣔ ᖿ ⣽ ⬊ ࡢ ᥋ ╔ ᩘ ࢆ ẚ ㍑ ࡋ ࠊࡑ ࡢ 㐪 ࠸ ࡽ ᚓ ࡽ ࢀ ࡓ
ࣃ ࢱ ࢺ ࢥ ࣮ ࢸ ࣥ ࢢ ࡢ ຠ ᯝ ࢆ ሗ ࿌ ࡋ ࡓ[ 3 6 ]ࠋ ᮏ ◊ ✲ ࡛ ࡣ ࠊ ྠ ࡌ ⣽ ⬊ ほ ᐹ ᡭ ἲ ࠊࡍ ࡞ ࢃ ࡕ ࠊⴠ ᑕ ᆺ ⺯ ග 㢧 ᚤ 㙾 ࡛ ⺯ ග Ⰽ ⣲ ࢆ ྲྀ ࡾ ㎸ ࢇ ࡔ 㛫 ⴥ ⣔ ᖿ ⣽ ⬊ ࡢ ᥋ ╔ ᵝ Ꮚ ࢆ ほ ᐹ ࡋ ࠊ ᙳ ࡋ ࡓ ࠋ
ࡉ ࡽ “image-pro”➼ ࡢ ⣽ ⬊ ᙧ ែ ⏬ ീ ฎ ⌮ ᑓ ⏝ ࡢ ᕷ ㈍ ࢯ ࣇ ࢺ ࢆ ⏝ ࠸ ࡿ ࡇ ࡛ ࠊ ⏕ య ᮦ ᩱ ᥋ ╔ ࡋ ࡓ ึ ᮇ ⣽ ⬊ ࡘ ࠸ ࡚ ᙧ ែ(㠃 ✚)࡞ ࡢ ࣃ ࣛ ࣓ ࣮ ࢱ ࢆ ⮬ ື ⓗ ᩘ ್ ࡍ ࡿ ࡇ ࡀ ࡛ ࡁ ࡿ ࠋ
ᮏ ◊ ✲ ࡛ 㛤 Ⓨ ࡋ ࡓ ホ ౯ ᢏ ⾡ ࡢ Ⅼ ࡋ ࡚ ձ ᧯ స ࡀ ⡆ ༢
ղ 100 ಶ ௨ ୖ ࡢ ⣽ ⬊ ࡀ 㐃 ⥆ ⓗ ほ ᐹ ࡛ ࡁ ࡿ ࡇ ࡛ 㸪 ホ ౯ ⤖ ᯝ ࡢ ୍ ⯡
ࡀ ࡛ ࡁ ࡿ
ࡇ ࡀ ᣲ ࡆ ࡽ ࢀ ࡿ ࠋ ୍ ᪉ 㸪 ホ ౯ ᢏ ⾡ ࡢ ᙅ Ⅼ ࡋ ࡚ 㸪
ձ ⣽ ⬊ ࡢ ᢞ ᙳ 㠃 ✚ ࢆ ほ ᐹ ࡍ ࡿ ࡓ ࡵ 㸪 ⏕ య ᮦ ᩱ ࡢ ⾲ 㠃 ≧ ែ ᐃ ್ ࡀ ᕥ ྑ ࡉ ࢀ ࡿ
ղ 㠃 ✚ ⏬ ീ ࡢ ⥡ 㯇 ࡉ ࡣ ⣽ ⬊ ཌ ࡳ ᕥ ྑ ࡉ ࢀ ࡿ ࡇ ࡀ ᣲ ࡆ ࡽ ࢀ ࡿ ࠋ
1.3.4 ゎ ᯒ ᡭ 㡰
ձ ࢝ ࣛ ࣮ ⏬ ീ ࡽ ࣔ ࣀ ࢡ ࣟ ⏬ ീ ኚ ࡍ ࡿ㸦 ࡣ ࡌ ࡵ ࡽ ࣔ ࣀ ࢡ ࣟ ⏬ ീ ࡛
࠶ ࢀ ࡤ ᚲ せ ࡞ ࠸ 㸧
ᐇ 㝿 ࡣ ࠊ ⦅ 㞟 ࣓ ࢽ ࣗ ࣮ ࡢ ኚ ࡛ 24 ࣅ ࢵ ࢺ ࢝ ࣛ ࣮ ࡛ ࠶ ࢀ ࡤ 8 ࣅ ࢵ ࢺ ࢢ ࣞ ࣮ ࢫ ࢣ ࣮ ࣝ ኚ ࡋ ࡓ ࠋ
ղ ᢳ ฟ
ᐃ ࣓ ࢽ ࣗ ࣮ ࡢ ࢝ ࢘ ࣥ ࢺ ࢧ ࢬ ࡛ ᡭ ື ᢳ ฟ ࢆ 㑅 ᢥ ࡋ ࡚ ᢳ ฟ ࣞ ࣥ ࢪ ࢆ タ ᐃ ࡍ ࡿ
URL ࣌ ࣮ ࢪ ࠊ
11 http://www.mediacy.jp/webhelp/count_size_general_operation.htm ࡢ 3B ࢆ ཧ ↷ ࠋ
ճ ࢝ ࢘ ࣥ ࢺ ࡛ ղ ࡛ タ ᐃ ࡋ ࡓ ᢳ ฟ ࣞ ࣥ ࢪ ࡢ ≀ ࡀ ࡚ ᢳ ฟ ࡉ ࢀ ࡿ
ཧ ↷ ࡋ ࡓ ࠸ ⣽ ⬊㸦 ᢳ ฟ ࡉ ࢀ ࡓ 㸧ࢆ ࢲ ࣈ ࣝ ࢡ ࣜ ࢵ ࢡ ࡍ ࡿ ࡇ ࡛ ᐃ ್ ࡀ
⾲ ♧ ࡉ ࢀ ࡿ
๐ 㝖 ࡋ ࡓ ࠸ ⏬ ീ ࡣ ࢲ ࣈ ࣝ ࢡ ࣜ ࢵ ࢡ ࡛ ๐ 㝖 㡯 ┠ ࡀ ࡛ ࡿ ࠋࢳ ࢙ ࢵ ࢡ ࡍ ࡿ ࡇ
࡛ ๐ 㝖 ࡛ ࡁ ࡿ ࠋࡲ ࡓ ࠊࢹ ࣮ ࢱ ࡢ ୍ ぴ ⾲ ♧ ࡣ ࢝ ࢘ ࣥ ࢺ ࢧ ࢬ ࡢ ⾲ ♧ ࡛ ᐃ ࢹ ࣮ ࢱ ࢆ 㑅 ᢥ ࡍ ࡿ ࡇ ࡛ ྍ ⬟ ࠋ
1.3.5 ⣽ ⬊ ึ ᮇ ᥋ ╔ 㠃 ✚
ᅗ 1.4. ᆺ ⓗ ࡞ ⣽ ⬊ ึ ᮇ ᥋ ╔ 㠃 ✚ ศ ᕸ ࡢ
ᅗ 1.4 ♧ ࡋ ࡓ ࡼ ࠺ ࠊ⏕ య ᮦ ᩱ ୖ ࠾ ࡅ ࡿ ࡚ ࡢ ⣽ ⬊ ࡣ ࠶ ࡿ 㝈 ࡽ ࢀ ࡓ
⠊ ᅖ ࡢ ึ ᮇ ᥋ ╔ 㠃 ✚ ್ 㞟 ୰ ࡋ ࠊࡑ ࡢ ᚋ ῶ ᑡ ࡍ ࡿ ഴ ྥ ࡀ ぢ ࡽ ࢀ ࡿ ࠋࡑ ࡇ ࡛ ᮏ ◊ ✲ ࡛ ࡣ ࠊ ⣽ ⬊ ึ ᮇ ᥋ ╔ 㠃 ✚ ࢆ 350ȝm2 ࡽ 3500ȝm2 ࡲ ࡛ タ ᐃ ࡋ ࠊ ᖹ ᆒ ್ ཬ ࡧ ㄗ ᕪ ࢆ ồ ࡵ ࡿ ࠋồ ࡵ ࡓ ᖹ ᆒ ್ ࡽ ㄗ ᕪ ࢆ ᘬ ࠸ ࡓ ್ ࡣ ⣽ ⬊ ึ ᮇ ᥋
╔ 㠃 ✚ ࡢ ᭱ ᑠ ್ ࡋ ࡚ ᥇ ⏝ ࡋ ࠊồ ࡵ ࡓ ᖹ ᆒ ್ ࡽ ㄗ ᕪ ࢆ ㊊ ࡋ ࡓ ್ ࡣ ⣽ ⬊ ึ ᮇ ᥋ ╔ 㠃 ✚ ࡢ ᭱ ್ ࡋ ࡚ ᥇ ⏝ ࡍ ࡿ ࠋࡉ ࡽ ࠊ ᐃ ࡋ ࡓ ⣽ ⬊ ึ ᮇ ᥋ ╔ 㠃 ✚ ࡢ ࢹ ࣮ ࢱ ࡼ ࡾ ࠊ ᖹ ᆒ ್ ཬ ࡧ ㄗ ᕪ ࢆ ồ ࡵ ࡿ ࠋ
0 20 40 60 80 100 120 140160 180
cell count
cell attachment area
12
➨ 2 ❶ 㝧 ᴟ 㓟 ࢳ ࢱ ࣥ ࣆ ࣥ ୖ ࡢ ⧄ ⥔ ⱆ ⣽ ⬊ ᡂ 㛗 ᅉ Ꮚ(FGF)-2/ ࣃ ࢱ
ࢺ 」 ྜ ᒙ ࡢ ᙧ ᡂ 2.1 ⥴ ゝ
2.1.1 ◊ ✲ ┠ ⓗ
⧄ ⥔ ⱆ ⣽ ⬊ ᡂ 㛗 ᅉ Ꮚ(௨ ୗ ࠊFGF-2 グ ࡍ)ࡣ ࠊ ⓶ ⤌ ⧊ ࠊ ⾑ ⟶ ࠊ 㦵 ⤌
⧊ ࡞ ከ ᒱ ࢃ ࡓ ࡿ ⤌ ⧊ ࡢ ⏕ ࢆ ಁ 㐍 ࡍ ࡿ ຠ ᯝ ࡀ ࠶ ࡿ ࡓ ࡵ ࠊ ㏆ ᖺ ࠊ ་ ⒪ ᛂ ⏝ ࡢ ◊ ✲ ࡀ ┒ ࢇ ⾜ ࢃ ࢀ ࡚ ࠸ ࡿ ⏕ య ά ᛶ ≀ ㉁ ࡢ ࡦ ࡘ ࡛ ࠶ ࡿ ࠋ FGF-2 ࡢ ⓶ ⤌ ⧊ ⏕ ⬟ ࡣ ࠊ⛉ ◊ 〇 ⸆ ᰴ ᘧ ♫ ࡼ ࡾ ᕷ ㈍ ࡉ ࢀ ࡚ ࠸ ࡿ 〟
⒪ ⸆(ࣇ ࣈ ࣛ ࢫ ࢺ ࢫ ࣉ ࣞ ࣮)࡛ ᪤ ⏝ ࡉ ࢀ ࡚ ࠾ ࡾ ࠊ ࡉ ࡽ ྠ ♫ ࡼ ࡗ ࡚ ⌧ ᅾ ࠊ 㦵 ⤌ ⧊ ࡸ ㌾ 㦵 ⤌ ⧊ ࡢ ⏕ ࢆ ಁ 㐍 ࡍ ࡿ ⸆ ရ ࡋ ࡚ ࡶ ⮫ ᗋ ◊ ✲ ࡀ 㐍 ࡵ ࡽ ࢀ ࡚ ࠸ ࡿ ࠋࡇ ࡢ FGF-2 ࡣ య ෆ ࡛ ᛴ ㏿ ᣑ ᩓ ࠊኻ ά ࡍ ࡿ ࡓ ࡵ ࠊຠ ᯝ ࡢ ᣢ ⥆ ࡢ ࡓ ࡵ ᩿ ⥆ ⓗ ࡞ 㔞 ᢞ ࡀ ᚲ せ ࡞ ࡿ ࠋࡑ ࡇ ࡛ ࠊFGF-2 ࢆ ఱ ࡽ
ࡢ ᇶ ᮦ ᅛ ᐃ ࡋ ࠊ 㝖 ᨺ ࡉ ࡏ ࡿ ࡇ ࡼ ࡗ ࡚ ኻ ά ࢆ 㜵 ࡂ ࡘ ࡘ ຠ ᯝ ࢆ ᣢ
⥆ ࡉ ࡏ ࡿ ࠸ ࠺ ࢹ ࡣ ௨ ๓ ࡽ ◊ ✲ ࡉ ࢀ ࡚ ࡁ ࡓ[ 3 7 - 4 0 , 5 6 ]ࠋࡑ ࠺ ࡋ ࡓ
◊ ✲ ࡢ ෆ ࠊFGF-2 ࢆ 㐣 㣬 ࣜ ࣥ 㓟 ࢝ ࣝ ࢩ ࢘ ࣒ ⁐ ᾮ ῧ ຍ ࡋ ࠊඹ ỿ ࡼ ࡗ
࡚ ᇶ ᮦ ᢸ ᣢ ࡉ ࡏ ࡿ ࠸ ࠺ ᪉ ἲ ࡀ ࠊ ⊂ ❧ ⾜ ᨻ ἲ ே ⏘ ᴗ ᢏ ⾡ ⥲ ྜ ◊ ✲ ᡤ ࠊ
ఀ ⸨ ࡽ ࡼ ࡗ ࡚ 㛤 Ⓨ ࡉ ࢀ ࡚ ࠸ ࡿ ࠋ ఀ ⸨ ࡽ ࡣ ࠊ Ỉ 㓟 ࣃ ࢱ ࢺ ࢭ ࣛ ࣑ ࢵ ࢡ
[ 4 0 ]ࡸ ⾲ 㠃 ࢆ 㝧 ᴟ 㓟 ฎ ⌮ ࡋ ࡓ ࢳ ࢱ ࣥ[ 5 6 ]ࢆ ᇶ ᮦ ࡋ ࡓ ◊ ✲ ࢆ ⾜ ࠸ ࠊ ࠸ ࡎ
ࢀ ࡢ ᇶ ᮦ ࡶ ⮫ ᗋ ᛂ ⏝ ࡀ ㄆ ࡵ ࡽ ࢀ ࡚ ࠸ ࡿ ་ ⒪ ⏝ ㍺ ᾮ ࢆ ΰ ྜ ࡋ ࡓ ᚓ ࡽ ࢀ ࡿ
ࣜ ࣥ 㓟 ࢝ ࣝ ࢩ ࢘ ࣒ 㐣 㣬 ⁐ ᾮ ࢆ ⏝ ࠸ ࡚ FGF-2 ࡀ ࣜ ࣥ 㓟 ࢝ ࣝ ࢩ ࢘ ࣒ ࡢ ඹ ỿ ࡛ ᢸ ᣢ ྍ ⬟ ࡛ ࠶ ࡿ ࡇ ࠊࡉ ࡽ ᢸ ᣢ ᚋ ࡢ FGF-2 ࡀ ኻ ά ࡋ ࡚ ࠸ ࡞
࠸ ࡇ ࢆ ᫂ ࡽ ࡋ ࡓ ࠋ ≉ ࠊ ᚋ ⪅ ࡢ ◊ ✲ ࡛ ⏝ ࠸ ࡽ ࢀ ࡓ 㝧 ᴟ 㓟 ฎ ⌮ ࢳ ࢱ ࣥ ࡣ ࠊ 㦵 ᢡ ⒪ ࡢ ୍ ᡭ ἲ ࡛ ࠶ ࡿ እ 㦵 ᢡ ᅛ ᐃ ⏝ ࠸ ࡿ ල ࡢ ⣲ ᮦ ࡋ
࡚ ࡶ ⏝ ࡉ ࢀ ࡚ ࠾ ࡾ ࠊFGF-2 ࡢ ᢸ ᣢ ࡼ ࡗ ࡚ ⤒ ⓶ ᇙ ධ ࡉ ࢀ ࡓ ල ࿘ ㎶ ࡢ 㦵 ⤌ ⧊ ࠶ ࡿ ࠸ ࡣ ⓶ ⤌ ⧊ ࡢ ⏕ ࢆ ಁ 㐍 ࡋ ࠊ እ 㦵 ᢡ ᅛ ᐃ ࡛ ၥ 㢟 ࡞ ࡗ ࡚
࠸ ࡿ ᤄ ධ ㊰ ឤ ᰁ 㜵 Ṇ ᭷ ຠ ࡛ ࠶ ࡿ ࡇ ࡀ ື ≀ ᐇ 㦂 ࡼ ࡗ ࡚ ᫂ ࡽ ࡞ ࡗ
ࡓ[ 5 5 ]ࠋࡋ ࡋ ࠊ⌧ ᅾ ሗ ࿌ ࡉ ࢀ ࡚ ࠸ ࡿ 㝧 ᴟ 㓟 ฎ ⌮ ࢳ ࢱ ࣥ ⾲ 㠃 ࡢ FGF-2
ࡢ ඹ ỿ ᢸ ᣢ 㔞 ᭱ 㐺 ᮲ ௳ ࡣ 37 Υ ࡛ 48 㛫 ಖ ᣢ ࡍ ࡿ ࠸ ࠺ ⏕ య ≀ ㉁ ࡣ 㐣 㓞 ࡞ ᮲ ௳ ࡛ ࠊFGF-2 ࡢ ኻ ά ⋡ ࢆ ⪃ ៖ ධ ࢀ ࡿ 㠀 ᖖ 㠀 ຠ ⋡ ࡞ ᢸ ᣢ ᪉ ἲ ࡛ ࠶ ࡾ ࠊᨵ ၿ ࡢ వ ᆅ ࡀ ࠶ ࡿ ⪃ ࠼ ࡽ ࢀ ࡿ ࠋ⁐ ゎ ࡋ ࡓ FGF-2 ࡀ ኻ ά ࡋ
࡞ ࠸ 㝈 ⏺ ᮲ ௳ ࡀ 25 Υ ࡛ 24 㛫 ࡉ ࢀ ࡚ ࠾ ࡾ ࠊᑡ ࡞ ࡃ ࡶ ࡇ ࡢ ᮲ ௳ ෆ ࡛ FGF-2 ࢆ ᢸ ᣢ ࡍ ࡿ ࡇ ࡼ ࡾ ࠊኻ ά ⋡ ࢆ ప ῶ ࡉ ࡏ ࡿ ࡇ ࡀ ྍ ⬟ ࡛ ࠶ ࡿ
⪃ ࠼ ࡽ ࢀ ࡿ ࠋ ୍ ᪉ ࡛ ࠊ ప ࡛ ࡣ ࣜ ࣥ 㓟 ࢝ ࣝ ࢩ ࢘ ࣒ ࡢ ᯒ ฟ ㏿ ᗘ ࡀ ప ୗ ࡋ ࠊ
༑ ศ 㔞 ࡢ FGF-2 ࡢ ᢸ ᣢ ࡀ ᮃ ࡵ ࡞ ࠸ ࡇ ࡶ ␃ ព ࡍ ࡿ ᚲ せ ࡀ ࠶ ࡿ ࠋ
ࡑ ࡇ ࡛ ᮏ ◊ ✲ ࡛ ࡣ ࠊFGF-2 ά ᛶ ࢆ ⥔ ᣢ ࡋ ࡘ ࡘ ᐊ ࠊ24 㛫 ࡛ FGF-2
ࢆ 㝧 ᴟ 㓟 ฎ ⌮ ࢳ ࢱ ࣥ ୖ ᢸ ᣢ ࡍ ࡿ ᢏ ⾡ ࡢ ☜ ❧ ࢆ ⾜ ࡗ ࡓ ࠋ ල య ⓗ ࡣ ࠊ
13
➨ ୍ ࣜ ࣥ 㓟 ࢝ ࣝ ࢩ ࢘ ࣒ ࡢ ⤖ ᬗ ᡂ 㛗 ࡢ ᰾ ࡋ ࡚ ⾲ 㠃 ࣜ ࣥ 㓟 ࢝ ࣝ ࢩ ࢘ ࣒ ᒙ ࢆ ᙧ ᡂ ࡍ ࡿ ๓ ฎ ⌮ ࡢ ᭱ 㐺 ᮲ ௳ ࢆ Ỵ ᐃ ࡋ ࠊ ➨ ๓ ฎ ⌮ ࡀ FGF-2-ࣜ ࣥ 㓟 ࢝ ࣝ ࢩ ࢘ ࣒ 」 ྜ ᒙ ࡢ స 〇 ࡶ ࡓ ࡽ ࡍ ຠ ᯝ(」 ྜ ᒙ ࡢ ࡛ ࡁ ࡸ ࡍ ࡉ) ࡘ ࠸
࡚ ᳨ ウ ࡍ ࡿ ࡇ ࢆ ┠ ⓗ ࡋ ࡓ ࠋ ࡉ ࡽ ➨ ୕ ࡋ ࡚ ࠊ ᢸ ᣢ ࡉ ࢀ ࡓ FGF-2 ࡢ ά ᛶ ホ ౯ ࢆ ⣽ ⬊ ᇵ 㣴 ᐇ 㦂 ࡼ ࡗ ࡚ ⾜ ࡗ ࡓ ࠋ ௨ ୖ ࡢ ◊ ✲ ⤖ ᯝ ࢆ ⥲ ྜ ࡍ ࡿ ࡇ ࡼ ࡗ ࡚ ࠊFGF-2 ࢆ ኻ ά ࡉ ࡏ ࡎ ຠ ⋡ ࡼ ࡃ ඹ ỿ ᢸ ᣢ ࡛ ࡁ ࡿ ᪂ つ ࡢ ᡭ ἲ ࢆ ☜ ❧ ࡛ ࡁ ࡿ ࡶ ࡢ ᮇ ᚅ ࡛ ࡁ ࡿ ࠋ
2.1.2 ◊ ✲ ⫼ ᬒ
་ ⒪ ⌧ ሙ ࡣ 㐍 ࡋ ࠊ ᭱ ㏆ ࡛ ࡣ 㛤 ᨺ 㦵 ᢡ ࡸ ⢊ ○ 㦵 ᢡ ࡶ ᑐ ᛂ ࡛ ࡁ ࡿ እ 㦵 ᢡ ᅛ ᐃ ࡤ ࢀ ࡿ 㦵 ᢡ ⒪ ἲ ࢆ ⏝ ࠸ ࡿ ࢣ ࣮ ࢫ ࡀ ᖺ ⋡ 3 㸣 ࡛ ቑ ຍ ࡋ ࡚
࠸ ࡿ ࠋ እ 㦵 ᢡ ᅛ ᐃ ࡣ 㛗 㦵 ࡢ 㦵 ᢡ 㒊 ࢆ ᣳ ࡴ ⨨ 㔠 ᒓ ࡢ ࣆ ࣥ ࢆ ⤒
⓶ ⓗ (⓶ ࢆ ㈏ ㏻ ࡋ ࡚)ᤄ ධ ࡋ ࠊ ࡑ ࡢ ࣆ ࣥ ࢆ య እ ࡛ ᅛ ᐃ ࡍ ࡿ ࡇ ࡼ ࡗ
࡚ ⾜ ࠺ ప く ࡢ 㦵 ᢡ ⒪ ᪉ ἲ ࡛ ࠶ ࡾ ࠊ ࣜ ࣁ ࣅ ࣜ ࡢ ⛣ ⾜ 㛫 ࡀ ▷ ࡃ ࡚ ῭
ࡴ ࡞ ࡢ ≉ 㛗 ࡀ ࠶ ࡿ 㠃 ࠊ ᡭ ⾡ ᚋ ࡢ ࣆ ࣥ ⓶ ⏺ 㠃 ࡢ ᤄ ධ ㊰ ࢆ ㏻ ࡌ ࡚ ㉳ ࡇ ࡿ 㧗 ⋡(10.0㹼53.3 %)࡞ ⣽ ⳦ ឤ ᰁ ࠊ ࠸ ࢃ ࡺ ࡿ ࢺ ࣥ ࢿ ࣝ ឤ ᰁ ࡀ ၥ 㢟 ࡞ ࡗ ࡚ ࠸ ࡿ ࠋ ࡇ ࡢ ⣽ ⳦ ឤ ᰁ ࡢ せ ᅉ ࡣ ⤒ ⓶ ⓗ ᇙ ධ ࡍ ࡿ ࣆ ࣥ 㦵 ࡢ ⤖ ྜ ᙉ ᗘ ཬ ࡧ ⓶ ࡢ ᥋ ╔ ᙉ ᗘ ࡢ ప ࡉ ࡛ ࠶ ࡿ ࠋ 㦵 ᅛ ╔ ᙉ ᗘ ࢆ ୖ ࡆ ࡿ ࡓ ࡵ ࡣ
ࣆ ࣥ ࡢ ⾲ 㠃 㦵 ⤖ ྜ ࡍ ࡿ ࣃ ࢱ ࢺ ࢆ ࢥ ࣮ ࢸ ࣥ ࢢ ࡍ ࡿ ࡇ (➨ ୡ ௦ 㦵 ᢡ ᅛ ᐃ ල)ࡀ ຠ ᯝ ⓗ ࡛ ࠶ ࡾ[ 4 1 - 4 3 ]ࠊ ឤ ᰁ 㜵 Ṇ ຠ ᯝ ࡋ ࡚ ࡣ ᢠ ⳦ ⸆ ᢞ
㝔 ෆ እ ࡛ ࡢ ᪥ ᖖ ⓗ ࣆ ࣥ ࢣ ࡀ ᭱ ࡶ ຠ ᯝ ⓗ ࡉ ࢀ ࡚ ࡁ ࡓ[ 4 4 - 4 6 ]ࠋ ࡋ ࡋ ࠊ
ࣃ ࢱ ࢺ ࢥ ࣮ ࢸ ࣥ ࢢ ࡢ ┤ ᥋ ⓗ ឤ ᰁ 㜵 Ṇ ຠ ᯝ ࡣ 㝈 ᐃ ⓗ ࡛ ࠶ ࡾ ࠊ ᢠ ⳦ ⸆
ࡸ ᪥ ᖖ ⓗ ࣆ ࣥ ࢣ ࡣ ⤌ ⧊ ࡢ ࣆ ࣥ ࡢ ᐦ ╔ ࢆ ಁ ࡍ ࡶ ࡢ ࡛ ࡣ ࡞ ࠸ ࠋ ࡉ ࡽ 㝔 ෆ እ ࡛ ࡢ እ ᅛ ᐃ ჾ ල ࢣ ࡣ ᝈ ⪅ ࡢ QOL(Quality of life)ࢆ ప ୗ ࡉ ࡏ ࠊ
┳ ㆤ ᖌ ࡢ ㆤ ㈇ ᢸ ࢆ ᙉ ࠸ ࡿ ⤖ ᯝ ࡞ ࡗ ࡚ ࠸ ࡿ ࠋ
ࡇ ࠺ ࡋ ࡓ ୰ ࠊ⏘ ⥲ ◊ ࡛ ࡣ ࠊࠕ ᮦ ᩱ ⏕ య ෆ ᇙ ධ ࡍ ࡿ ᮦ ᩱ ⮬ ㌟ ࡀ ⣽ ⬊ ศ ࡸ ⤌ ⧊ ⏕ ࢆ ಁ ࡀ ࡍ ࠖ⏕ య ᮦ ᩱ[ 4 7 ]࡛ ࠶ ࡿࠕ ➨ ୕ ୡ ௦ ⏕ య ᮦ ᩱ ࠖࡢ 㛤
Ⓨ ࢆ ᛕ 㢌 ⨨ ࡁ ࠊ ࡇ ࢀ ࢆ ⏕ ་ ⒪ ࡢ ⤒ ῭ ⓗ ᢏ ⾡ ⓗ ၥ 㢟 ࢆ ⿵ ࠺ ᪉ ἲ ࡋ ࡚ ᥦ ၐ ࡋ ࡓ ࠋ ࡑ ࢀ ࡼ ࢀ ࡤ ࠊ ከ ࡃ ࡢ ⏕ య ᮦ ᩱ ࡣ ࠊ ⏕ ≀ Ꮫ ⓗ ά ᛶ ᅉ Ꮚ ࢆ ኚ ᛶ ࡉ ࡏ ࡎ ⾲ 㠃 ᢸ ᣢ ࡍ ࡿ ࡇ ࡛ ➨ ୕ ୡ ௦ ࡀ ྍ ⬟ ࡛ ࠶ ࡿ ࠋ ࡑ ࡢ ⪃ ࠼ ᇶ
࡙ ࡁ ࠊ ⓶ ⤌ ⧊ 㦵 ⤌ ⧊ ࡢ ⏕ ࢆ ಁ ࡀ ࡍ ⏕ ≀ Ꮫ ⓗ ά ᛶ ᅉ Ꮚ ࢆ ᢸ ᣢ ࡉ ࡏ ࡓ ➨ ୕ ୡ ௦ እ 㦵 ᢡ ᅛ ᐃ ල ࢆ 㛤 Ⓨ ࡍ ࢀ ࡤ ࠊ እ 㦵 ᢡ ᅛ ᐃ ⾡ ࡛ ၥ 㢟 ࡞ ࡿ
⓶ ⏺ 㠃 ࡛ ࡢ ࢺ ࣥ ࢿ ࣝ ឤ ᰁ ࢆ ⓗ ᢚ ไ ࡛ ࡁ ࡿ ࡶ ࡢ ᮇ ᚅ ࡉ ࢀ ࡿ ࠋ
⏕ ≀ Ꮫ ⓗ ά ᛶ ᅉ Ꮚ ࡢ ከ ࡃ ࡣ ࢱ ࣥ ࣃ ࢡ ࡽ ࡞ ࡿ ࡓ ࡵ ࠊ ఀ ⸨ ࡽ(⏘ ⥲ ◊) ࡣ ࠊ 㦵 ࡸ ṑ ࡢ ᡂ ศ ࡛ ࠶ ࡿ ࣜ ࣥ 㓟 ࢝ ࣝ ࢩ ࢘ ࣒ ࡢ ࢱ ࣥ ࣃ ࢡ ྾ ╔ ⬟ ╔ ┠ ࡋ ࠊ
ࣜ ࣥ 㓟 ࢝ ࣝ ࢩ ࢘ ࣒ ࢼ ࣀ ࢡ ࣛ ࢫ ࢱ ࣮ ྜ య ࡢ LJ 㟁 ࢆ ไ ᚚ ࡋ ࡚ ࢱ ࣥ ࣃ ࢡ
14
ࡢ ඹ ỿ ᛂ ࢆ ㉳ ࡇ ࡋ ࠊ ✀ ࠎ ࡢ ே ᕤ ᮦ ᩱ ᢸ ᣢ ࡉ ࡏ ࡿ ᪉ ἲ ࢆ ◊ ✲ 㛤 Ⓨ ࡋ ࡚
ࡁ ࡓ[ 4 8 - 5 5 ]ࠋ ࡇ ࡢ ᡭ ἲ ࢆ ⏝ ࠸ ࡿ ࠊ ᡂ 㛗 ᅉ Ꮚ ࠊ ⣽ ⬊ ᥋ ╔ ᅉ Ꮚ ࠊ ࢥ ࣛ ࣮ ࢤ ࣥ
࡞ ࡢ ࢱ ࣥ ࣃ ࢡ ㉁ ௨ እ ࡶ DNA ࡸ ࣅ ࢱ ࣑ ࣥ ➼ ࢆ ᢸ ᣢ ࡉ ࡏ ࡿ ࡇ ࡀ ྍ ⬟
࡛ ࠶ ࡿ ࠋ ≉ ࠊ ⓶ ࡸ 㦵 ࡢ ⤌ ⧊ ⏕ ࢆ ಁ 㐍 ࡍ ࡿ ᡂ 㛗 ᅉ Ꮚ ࡢ ୍ ✀ ࡛ ࠶ ࡿ ⧄
⥔ ⱆ ⣽ ⬊ ᡂ 㛗 ᅉ Ꮚ-2(௨ ୗ FGF-2 グ ࡍ)ࢆ ་ ⒪ ⏝ ㍺ ᾮ ࡢ ΰ ྜ ࡼ ࡗ ࡚ ᚓ
ࡽ ࢀ ࡿ ࣜ ࣥ 㓟 ࢝ ࣝ ࢩ ࢘ ࣒ 㐣 㣬 ⁐ ᾮ ΰ ྜ ࡉ ࡏ ࡓ ⁐ ᾮ ࢳ ࢱ ࣥ 〇 ⤒ ⓶ 㦵 ᢡ ᅛ ᐃ ල(௨ ୗ ࢳ ࢱ ࣥ ࣆ ࣥ)ࢆ ᾐ ₕ ࡍ ࡿ ࡇ ࡼ ࡗ ࡚ ࠊFGF-2- ࣃ ࢱ ࢺ
」 ྜ ⓶ ⭷(AP-FGF)ࢆ స 〇 ࡍ ࡿ ࡇ ᡂ ຌ ࡋ ࡓ ࠋ ࡇ ࡢ ࡼ ࠺ ᢸ ᣢ ࡉ ࢀ ࡓ FGF-2 ࡣ ࠊin vitro ᐇ 㦂 ࡼ ࡗ ࡚ ༑ ศ ࡞ ά ᛶ ࢆ ṧ ࡋ ࡚ ࠸ ࡿ ࡇ ࡀ ♧ ࡉ ࢀ ࡓ ࠋ ࡉ ࡽ ࠊAP-FGF ࢥ ࣮ ࢸ ࣥ ࢢ ࢳ ࢱ ࣥ ࣆ ࣥ ࢆ 1 ࣨ ᭶ ࢘ ࢧ ࢠ ⬯ 㦵 ⤒
⓶ ⓗ ᇙ ධ ࡋ ࡓ ࡇ ࢁ ࠊFGF-2 ࡣ 㦵 ᅛ ╔ ⓶ ⏕ ࢆ ྠ ಁ 㐍 ࡋ ࠊ㏻
ᖖ ࡛ ࡣ ⓶ ࡢ ᐦ ╔ Ⰻ ࡛ 94 㸣 ࡀ ⓶ -ࣆ ࣥ ⏺ 㠃 ࡛ ࢺ ࣥ ࢿ ࣝ ឤ ᰁ ࢆ ⏕ ࡌ
ࡿ ཝ ࡋ ࠸ ⎔ ቃ ࡛ ࡶ ࠊ ᢠ ⳦ ࡢ ᢞ ධ ࡞ ࡋ ࠊ ឤ ᰁ ⋡ ࢆ 44 㸣 ᢚ ࠼ ࡿ ࡇ ࡀ ศ ࡗ ࡓ[ 5 6 ]ࠋ
ࡋ ࡓ ࡀ ࡗ ࡚ ࠊAP-FGF ࢥ ࣮ ࢸ ࣥ ࢢ ࡋ ࡓ ࢳ ࢱ ࣥ ࣆ ࣥ ᢠ ⳦ ⸆ ᢞ ධ ࢆ ⤌
ࡳ ྜ ࢃ ࡏ ࢀ ࡤ ࠊ እ 㦵 ᢡ ᅛ ᐃ ⾡ ࡛ ၥ 㢟 ࡞ ࡿ ⓶ ⏺ 㠃 ࡛ ࡢ ⣽ ⳦ ឤ ᰁ ࢆ ຠ ᯝ ⓗ 㜵 Ṇ ࡛ ࡁ ࡿ ࡇ ࡀ ᮇ ᚅ ࡉ ࢀ ࡿ ࠋ
ࡋ ࡋ ࡞ ࡀ ࡽ ࠊ ࡇ ࢀ ࡲ ࡛ ࢳ ࣕ ࣥ ࣆ ࢜ ࣥ ࢹ ࣮ ࢱ ࡀ ᚓ ࡽ ࢀ ࡚ ࠸ ࡿ AP-FGF ࢥ ࣮ ࢸ ࣥ ࢢ ࡋ ࡓ ࢳ ࢱ ࣥ ࣆ ࣥ ࡣ ࠊ37 Υ ࠊ48 㛫 ࠸ ࠺ FGF-2
ࡗ ࡚ ࡣ 㐣 㓞 ࡞ ᮲ ௳ ࡛ ฎ ⌮ ࡉ ࢀ ࡚ ࠸ ࡿ ࡓ ࡵ ࠊ ฎ ⌮ ୰ ኻ ά ࡋ ࡚ ࡋ ࡲ ࠺ ศ Ꮚ ࡢ 㔞 ࡀ 㝿 ❧ ࡗ ࡚ ከ ࡃ ࠊ90 㸣 ௨ ୖ ࡢ ኻ ά ⋡ ࠸ ࠺ ᥎ ⟬ ࡀ ࡞ ࡉ ࢀ ࡚ ࠸
ࡿ ࠋᢸ ᣢ ࡉ ࢀ ࡚ ࠸ ࡿ FGF-2 ࡢ ෆ ࠊṇ 10 㸣 ⛬ ᗘ ࡋ ᭷ ຠ ⏝ ࡉ ࢀ ࡞
࠸ ࠸ ࠺ ࡢ ࡣ 㠀 ຠ ⋡ ࡛ ࠶ ࡾ ࠊࡇ ࡢ FGF-2 ᢸ ᣢ ᢏ ⾡ ࡣ ࡲ ࡔ ᨵ ၿ ࡢ వ ᆅ ࡀ
࠶ ࡿ ⪃ ࠼ ࡽ ࢀ ࡿ ࠋ ࡑ ࡢ ୰ ࡣ ⏝ ࡍ ࡿ ་ ⒪ ⏝ ㍺ ᾮ ࡢ ⤌ ࡳ ྜ ࢃ ࡏ ࡶ ྵ ࡲ
ࢀ ࡿ ࠋ
2.1.3 እ 㦵 ᢡ ᅛ ᐃ
2.1.3.1 እ 㦵 ᢡ ᅛ ᐃ ࡣ
ୖ ㏙ ࡢ ࡼ ࠺ ࠊ እ ᅛ ᐃ ࡣ ࠊ ⢊ ○ 㦵 ᢡ 㸦 ⢊ ࠎ ࡞ 㦵 ᢡ 㸧 ࡢ ࡼ ࠺ ᡭ ⾡
ࡼ ࡿ 㦵 ࡢ 㓄 ⨨ ࡀ ᅔ 㞴 ࡞ ሙ ྜ ࠊ 㛤 ᨺ 㦵 ᢡ 㸦 㦵 ࡀ ࠸ ࡗ ࡓ ࢇ ⓶ ࡢ እ ࡧ ࡔ ࡋ ࡓ 㦵 ᢡ 㸧 ࡢ ࡼ ࠺ 㦵 ᢡ 㒊 ࡀ ឤ ᰁ 㸦 ⮋ ࡍ ࡿ ࡇ 㸧 ࡋ ࡸ ࡍ ࡃ ┤ ᥋ ᡭ
⾡ ࡛ ࡁ ࡞ ࠸ ሙ ྜ ࠊ 㛵 ⠇ 㒊 ࡢ 㦵 ᢡ ࡢ ࡼ ࠺ 㦵 ᢡ ࡢ ᅛ ᐃ ࡀ ࡋ ࡃ ࠸ ሙ ྜ ࡞
ࡼ ࡃ ⏝ ࠸ ࡽ ࢀ ࡿ ࠋ እ ᅛ ᐃ ࡣ 㦵 ᢡ 㒊 ࢆ ┤ ᥋ ษ 㛤 ࡋ ࡞ ࠸ ࡢ ࡛ ࠊ 㦵 ࢲ
࣓ ࣮ ࢪ ࢆ ࠼ ࡎ 㦵 ᢡ 㒊 ࢆ ษ 㛤 ࡍ ࡿ ᡭ ⾡ ẚ 㦵 ᢡ ࡢ ࡾ ࢆ ᦆ ࡞ ࢃ ࡞ ࠸ ࠋ
እ ᅛ ᐃ ࡢ 㦵 ᢡ 㒊 ࢆ ࡣ ࡉ ࢇ ࡔ ୧ ഃ ࡢ 㦵 ࢿ ࢪ ࢆ ᩘ ᮏ ᤄ ධ ࡋ ࠊ 㦵 ᢡ 㒊 ࢆ ᘬ ࡗ ᙇ ࡗ ࡚ 㦵 ᢡ ࡢ ࡎ ࢀ ࢆ ࡛ ࡁ ࡿ ࡔ ࡅ ▹ ṇ ࡋ ࠊ ᨭ ࠼ ࡞ ࡿ 㔠 ᒓ 〇 ࡢ ᨭ ᰕ
15 㸦 እ ᅛ ᐃ ჾ ࠸ ࠺ 㸧࡛ 㦵 ᢡ ࢆ ᅛ ᐃ ࡍ ࡿ ሙ ྜ ࡶ ࠶ ࡿ ࠋ࣓ ࣜ ࢵ ࢺ ࡋ ࡚ ࡣ ࠊ య ෆ 㔠 ᒓ ࢆ ධ ࢀ ࡚ ␃ ࡵ ࡿ ࡢ ࡛ ࡣ ࡞ ࡃ య እ ࡛ ᅛ ᐃ ࡍ ࡿ ࡓ ࡵ ࠊ ᜦ ዲ ࡞
ࡿ ࡀ ࠊ ࢠ ࣉ ࢫ ࡛ ᅛ ᐃ ࡍ ࡿ ሙ ྜ ࡣ ␗ ࡞ ࡾ ᪩ ᮇ ࡽ ࣜ ࣁ ࣅ ࣜ ࡣ ࡛ ࡁ ࡿ ࡋ ࠊ 㔠 ᒓ ࢆ 㝖 ཤ ࡍ ࡿ ᡭ ⾡ ࡶ ⡆ ༢ ࡛ ࠶ ࡿ ࠋ
እ ᅛ ᐃ ࡼ ࡿ 㦵 ᢡ ࡢ ⒪ ࡣ Ṕ ྐ ⓗ ࡣ 1853 ᖺ ࡢ MALGAIGNEࡢ ∎ ᆺ እ ᅛ ᐃ ჾ ࡢ ⏝ ጞ ࡲ ࡾ ࠊྂ ࡃ ࡼ ࡾ ⏝ ࡀ ヨ ࡳ ࡽ ࢀ ࡚ ࡁ ࡓ ࠋ1907 ᖺ
ࡣ LAMBOTTE ࡀ ࣁ ࣮ ࣇ ࣆ ࣥ ࢆ ⏝ ࡍ ࡿ እ ᅛ ᐃ ჾ ࢆ ⪃ ࡋ ࡓ ࠋ ᪥ ᮏ
࡛ ࡶ 1925 ᖺ ྠ ᵝ ࡢ ๓ ⏣ ᘧ እ ᅛ ᐃ ჾ ࡀ ⪃ ࡉ ࢀ ࡓ ࠋ ⌧ ᅾ ࡛ ࡶ ⏝ ࡉ
ࢀ ࡚ ࠸ ࡿ HOFFMANN እ ᅛ ᐃ ჾ ࡣ 1935 ᖺ ࢫ ࢫ ࡛ ⪃ ࡉ ࢀ ࠊ ࣚ ࣮ ࣟ
ࢵ ࣃ ࡛ ከ ࡃ ࡢ ⮫ ᗋ ᛂ ⏝ ࡀ ⾜ ࢃ ࢀ ࡓ ࠋ
ࡇ ࡢ ࡼ ࠺ እ ᅛ ᐃ ἲ ࡣ ෆ ᅛ ᐃ ἲ ୪ ิ Ⓨ ᒎ ࡋ ࡚ ࠸ ࡓ ࡀ ࠊ ࣆ ࣥ ࢆ ⓶
㉁ 㦵 ⤒ ⓶ ⓗ ᇙ ධ ࡍ ࡿ ࡓ ࡵ ࠊ ࡑ ࡢ ᤄ ධ ㊰ ࡽ ࡢ ឤ ᰁ క ࠺ 㦵 㧊 ⅖ Ⓨ
࠸ ࠺ ᢠ ⏕ ≀ ㉁ Ⓨ ぢ ௨ ๓ ࡢ ་ Ꮫ ࡛ ࡣ ༑ ศ ᑐ ᛂ ࡛ ࡁ ࡞ ࠸ ྜ ే ࡀ ࠶ ࡿ ࡓ ࡵ ࠊ ḟ ➨ ࡑ ࡢ ⏝ 㢖 ᗘ ࡀ ᑡ ࡞ ࡃ ࡞ ࡗ ࡓ ࠋ
➨ ḟ ᡓ ᚋ ࠊ ᢠ ⏕ ≀ ㉁ ࡢ 㛤 Ⓨ ࠊ እ ᅛ ᐃ ჾ ࡢ ᨵ Ⰻ ࠊ ࡑ ࡋ ࡚ ࣆ ࣥ ࡢ ᨵ Ⰻ ࡼ ࡾ ࠊ ࣆ ࣥ ࡢ ᤄ ධ ㊰ ࡽ ࡢ ឤ ᰁ ࡼ ࡿ ༴ 㝤 ࡀ ᑡ ࡞ ࡃ ࡞ ࡗ ࡓ ࠋ ࡲ ࡓ ປ
ാ ⅏ ᐖ ࡸ ㏻ ᨾ ࡼ ࡿ 㧗 ࢚ ࢿ ࣝ ࢠ ࣮ እ യ ࡀ ቑ ࠼ ࡿ ᚑ ࠸ ࠊ ᚑ ᮶ ࡢ ෆ ᅛ ᐃ ἲ ࡛ ࡣ ᑐ ᛂ ࡛ ࡁ ࡞ ࠸ እ യ ࡀ Ⓨ ⏕ ࡋ ࠊ ᗘ እ ᅛ ᐃ ἲ ࡀ ぢ ┤ ࡉ ࢀ ࠊ 㝈 ᐃ
ⓗ 㐺 ᛂ ࡢ ࡶ ᗘ ⏝ ࡉ ࢀ ࡿ ࡼ ࠺ ࡞ ࡗ ࡓ ࠋ
୍ ᪉ ࠊ ᪧ ࢯ 㐃 ࢡ ࣝ ࢞ ࣥ ࡢ ILIZAROV ࡣ ࠊ 㦵 ᢡ ࡢ ᩚ ࠊ ᅛ ᐃ ᪩ ᮇ 㐠 ື
ࢆ ྍ ⬟ ࡍ ࡿ ILIZAROV እ ᅛ ᐃ ჾ ࢆ ⊂ ⮬ 㛤 Ⓨ ࡋ ࡓ ࠋࡇ ࡢ እ ᅛ ᐃ ჾ ࡣ 㦵 ᢡ ࡢ ᅛ ᐃ ࡢ ࡳ ࡛ ࡞ ࡃ ࠊ௬ 㦵 ᘏ 㛗 ࡼ ࡿ ᅄ ⫥ ᘏ 㛗 ࠊ㦵 ㌾ 㒊 ኚ ᙧ ࡢ ▹ ṇ ࠊ 㦵 ㌾ 㒊 Ḟ ᦆ ࡢ ⒪ ࡢ ࠸ ࡎ ࢀ ࡶ ⏝ ࡛ ࡁ ࠊ ࡢ እ ᅛ ᐃ ჾ ࡢ 㝈 ⏺ ࢆ ㉺ ࠼
ࡿ ⏬ ᮇ ⓗ ࡞ ࡶ ࡢ ࡛ ࠶ ࡗ ࡓ ࠋ ௬ 㦵 ᘏ 㛗 ࡸ 㦵 ⛣ ື ࡢ ᪉ ἲ ࡣ ࡇ ࡢ ᘏ 㛗 ჾ ጞ ࡲ
ࡾ ࠊ ⌧ ᅾ ⏝ ࡉ ࢀ ࡚ ࠸ ࡿ Orthofix እ ᅛ ᐃ ჾ ࡞ ᙳ 㡪 ࢆ ࠼ ࡚ ࠸ ࡿ ࠋ 2.1.3.2 እ 㦵 ᢡ ᅛ ᐃ ჾ ල
2.1.3.2.1 ࢳ ࢱ ࣥ ࢫ ࢡ ࣜ ࣗ ࣮
እ 㦵 ᢡ ᅛ ᐃ ࠾ ࠸ ࡚ ࠊ 㔠 ᒓ ࡣ ᵓ 㐀 ᮦ ᩱ ࡋ ࡚ ษ ࡞ ⣲ ᮦ ࡛ ࠶ ࡿ ࠋ ⏕ య ᮦ ᩱ ࡋ ࡚ ࡢ 㔠 ᒓ ᮦ ᩱ ࡢ Ḟ Ⅼ ࡣ ࠊ ⑂ ປ ࡼ ࡿ ◚ ቯ ࠊ ⭉ 㣗 ࡼ ࡗ ࡚ ᨺ ฟ ࡉ ࢀ ࡓ 㔠 ᒓ ࢜ ࣥ ࡢ ẘ ᛶ ࡀ ᣲ ࡆ ࡽ ࢀ ࠊ ࡉ ࡽ ே ᕤ 㛵 ⠇ ࡞ ࡢ ሙ ྜ ࡣ ྍ ື 㒊 ࡽ ࡢ ᦶ ⪖ ⢊ ࡢ ẘ ᛶ ࡞ ࡀ ⪃ ࠼ ࡽ ࢀ ࡿ ࠋ እ 㦵 ᢡ ᅛ ᐃ ࡣ ࢫ ࢸ ࣥ ࣞ ࢫ
ࡸ ࢳ ࢱ ࣥ ࡀ ⏝ ࡉ ࢀ ࡚ ࠸ ࡿ ࡀ ࠊ ᮏ ◊ ✲ ࡛ ᑐ ㇟ ࡍ ࡿ ࢳ ࢱ ࣥ 㛵 ࡋ ࡚ ゝ ཬ ࡍ ࢀ ࡤ ࠊ ẚ ㍑ ⓗ ㍍ ࡃ ᶵ Ე ᙉ ᗘ ࡶ ඃ ࢀ ࡚ ࠸ ࡿ ࠺ ࠼ ⏕ య ෆ ࡛ Ᏻ ᐃ ࡛ ࠶ ࡿ ࠋ ල య ⓗ ࡣ ࠊ ᮏ ◊ ✲ ࡛ ⏝ ࡍ ࡿ እ ᅛ ᐃ ࢳ ࢱ ࣥ ࢫ ࢡ ࣜ ࣗ ࣮(௨ ୗ ࡣ Ti ࣆ ࣥ
グ ࡍ)ࡣ 㝧 ᴟ 㓟 ⓶ ⭷ そ ࢃ ࢀ ࡿ ࡓ ࡵ ࠊ ാ ែ ࡍ ࡿ ≉ ᚩ ࡀ ࠶ ࡿ ࠋTi
16
ࣆ ࣥ ࡣ ⏕ య ෆ ▷ ᮇ 㛫 ࡋ Ꮡ ᅾ ࡏ ࡎ ࠊ ࡑ ࡢ ᮇ 㛫 ࡢ ࡳ య 㔜 ࡸ ά ື ࡼ ࡿ Ⲵ 㔜 ࢆ ⪏ ࠼ ࢀ ࡤ ࡼ ࠸ ࡓ ࡵ ࠊ ⭉ 㣗 ⑂ ປ ࠊ ࣇ ࣞ ࢵ ࢸ ࣥ ࢢ ⭉ 㣗 ⑂ ປ ࡞ ࡼ ࡿ
⏕ య ◚ ቯ ࢆ ㉳ ࡇ ࡍ ྍ ⬟ ᛶ ࡀ ᴟ ࡵ ࡚ ᑠ ࡉ ࠸ ࠋ ࡑ ࡋ ࡚ ࠊ ࡢ 㔠 ᒓ ࡢ ẚ 㔜 ࠊ ᙎ ᛶ ಀ ᩘ ࡢ ⣙ ༙ ศ ࡋ ࡞ ࠸ Ⅼ ࡽ ࠊ ࢳ ࢱ ࣥ 㔠 ᒓ ࡣ ẚ ᙉ ᗘ ࡀ ࡁ ࡃ ࠊ 㦵 ࡼ
ࡾ ㏆ ࠸ ᙎ ᛶ ಀ ᩘ ࢆ ࡶ ࡘ ඃ ࢀ ࡓ እ 㦵 ᢡ ᅛ ᐃ ᮦ ᩱ ࡶ ゝ ࠼ ࡿ ࠋ
2.1.3.2.2 እ 㦵 ᢡ ᅛ ᐃ ჾ ࡢ ✀ 㢮 ձ ∦ ഃ ᅛ ᐃ ᆺ unilateral type
ࣁ ࣮ ࣇ ࣆ ࣥ ࢆ ∦ ഃ ࡼ ࡾ ่ ධ ࡋ ࠊ ࡇ ࢀ ࢆ እ ᅛ ᐃ ჾ ࡛ ∦ ഃ ᅛ ᐃ ࡍ ࡿ ࠋ Orthofix እ ᅛ ᐃ ჾ ࣭AO እ ᅛ ᐃ ჾ ࣭CLYBURN እ ᅛ ᐃ ჾ ࡞ ྛ
✀ ࠶ ࡿ ࠋ ࠸ ࡎ ࢀ ࡶ 㛗 ㍈ ᪉ ྥ ࡛ ࡢ ᘏ 㛗 ࠊ ▷ ⦰ ࡀ ྍ ⬟ ࡛ ࠶ ࡿ ࠋ ╔ ᚋ ᒅ ᭤
࠾ ࡼ ࡧ ഃ ᪉ ㌿ ࢆ ᩚ ྍ ⬟ ࡞ ᅛ ᐃ ჾ ࡀ ከ ࠸ ࠋ ᅇ ᪕ ㌿ ࡣ ᩚ ࡛ ࡁ ࡞ ࠸ ࠋ
╔ ࡛ ࡁ ࡿ ࡔ ࡅ ㌿ ࢆ ᩚ ࡋ ࡚ ࠾ ࡃ ࡇ ࡀ ษ ࡛ ࠶ ࡿ ࠋ ղ ୧ ഃ ᅛ ᐃ ᆺ bilateral type
㈏ ㏻ ࣆ ࣥ ࢆ 2 ಶ ࡢ እ ᅛ ᐃ ჾ ࡛ ᨭ ᣢ ᅛ ᐃ ࡍ ࡿ ࠋHOFFMANN እ ᅛ ᐃ ჾ ࡀ య ⾲ ⓗ ࡛ ࠶ ࡿ ࠋ ᡭ ᣦ 㦵 ⏝ ࠸ ࡿ ⏕ ⏣ ᘧ እ ᅛ ᐃ ჾ ࡶ ࡇ ࡢ ศ 㢮 ᒓ ࡍ ࡿ ࠋ
ճ ༙ ᆺ semicircular type
እ ᅛ ᐃ ჾ ࡢ ࣇ ࣞ ࣮ ࣒ ࡀ ༙ ≧ ࡛ ࠊ㈏ ㏻ ࣆ ࣥ ࢆ ⏝ ࠸ ࡿ ࠋACE-FISHER
እ ᅛ ᐃ ჾ ࠊVOLKOV OGANESIAN እ ᅛ ᐃ ჾ ࡀ ࡇ ࡢ ᆺ ࡛ ࠶ ࡿ ࠋ մ ᆺ circular type
ILIZARO ࡢ እ ᅛ ᐃ ჾ ࡀ ࡼ ࡃ ▱ ࡽ ࢀ ࡿ ࠋ ๓ ㏙ ࡢ ࡼ ࠺ ᪧ ࢯ 㐃 ࡢ ILIZAROV ࡀ 1951 ᖺ 㛤 Ⓨ ࡋ ࡓ ࡀ ࠊす ഃ ㅖ ᅜ ࡣ 1981 ᖺ ௨ ᚋ ▱ ࡽ ࢀ ࡿ
ࡼ ࠺ ࡞ ࡗ ࡓ ࠋKIRSCHNER 㖡 ⥺ ࢆ ㈏ ㏻ ࣆ ࣥ ⏝ ࠸ ⥭ ᙇ ࢆ ᯈ ࣇ ࣞ ࣮
࣒ ୖ ࡛ ຍ ࠼ ࠊ ᅛ ᐃ ຊ ࢆ ྥ ୖ ࡉ ࡏ ࡿ ࠋ ㍈ ㌿ ࢆ ྵ ࡴ ࠶ ࡽ ࡺ ࡿ ㌿ ࠊ ኚ ᙧ
ࢆ ィ ⏬ ⓗ ᩚ ࡛ ࡁ ࡿ ࠋ ⏝ ࡣ ண ࡵ ୍ 㐃 ࡢ ㅮ ⩦ ࢆ ཷ ࡅ ࡿ ᚲ せ ࡀ ࠶ ࡿ ࠋ
2.1.3.2.3 እ ᅛ ᐃ ἲ ࡢ 㛗 ᡤ ▷ ᡤ 1 㸧 㛗 ᡤ
ձ ᑡ ࡞ ࠸ く ࡛ ᦆ യ 㒊 ࡼ ࡾ 㞳 ࢀ ࡚ ᅛ ᐃ ࡛ ࡁ ࡿ ࠋ ࡋ ࡓ ࡀ ࡗ ࡚ ෆ ᅛ ᐃ ࡀ ᅔ 㞴 ࡞ ⤌ ⧊ Ḟ ᦆ ࡸ ឤ ᰁ ࡀ ࠶ ࡿ 㛤 ᨺ 㦵 ᢡ ࠊ ഇ 㛵 ⠇ ࡼ ࠸ 㐺 ᛂ ࡀ ࠶ ࡿ ࠋ ࡲ ࡓ ㌟ ≧ ែ ၥ 㢟 ࡀ ࠶ ࡾ ࠊ ෆ ᅛ ᐃ ⾡ ࡢ く ࢆ ࡉ ࡏ ࡓ ࠸ ከ Ⓨ እ യ
ࡶ 㐺 ᛂ ࡛ ࡁ ࡿ ࠋ
ղ 㦵 ᢡ 㒊 く ࢆ ຍ ࠼ ࡞ ࠸ ࡓ ࡵ 㦵 ᢡ 㒊 ࡢ ⓶ ࠊ ➽ ⫗ ࠊ 㦵 ⭷ ࢆ ᭱ 㝈 Ꮡ ࡛ ࡁ ࡿ ࠋ ࡲ ࡓ 㦵 ᢡ 㒊 ෆ ᅛ ᐃ ᮦ ࡞ ࡢ ␗ ≀ ࢆ ␃ ⨨ ࡋ ࡞ ࠸ ࠋ
ճ 㛤 ᨺ ࠊ ឤ ᰁ ࡢ ≧ ែ ࡢ ほ ᐹ ࠊ ฎ ⨨ ࠊ ⓶ ᘚ ࡞ ࡢ ᳜ ⓶ ࠊ 㦵 ᡭ ⾡ ࡀ
17 እ ᅛ ᐃ ჾ ࢆ ࡘ ࡅ ࡓ ࡲ ࡲ ⾜ ࠼ ࡿ ࠋ
մ እ ᅛ ᐃ ჾ ࡼ ࡾ ࠊ 㦵 ᢡ 㒊 ࡢ ᅽ ㏕ ࠊ ≌ ᘬ ࡀ ࡅ ࡽ ࢀ ࡿ ࠋ ▷ ⦰ ᑐ ࡋ ࡚ ௬ 㦵 ᘏ 㛗 ⾡ ࡶ 㐺 ᛂ ࡛ ࡁ ࡿ ࠋ
յ እ ᅛ ᐃ ჾ ╔ ᚋ 㦵 ᢡ ࡢ ㌿ ࡢ ᩚ ࡀ ྍ ⬟ ࡛ ࠶ ࡿ ࠋ ն ᪩ ᮇ ࡢ 㞄 ᥋ 㛵 ⠇ ࡢ 㐠 ື ࢆ ྍ ⬟ ࡍ ࡿ ᅛ ᐃ ຊ ࡀ ᚓ ࡽ ࢀ ࡿ ࠋ շ ᢤ 㔥 ࡀ ෆ ᅛ ᐃ ࡃ ࡽ ᐜ ᫆ ࡛ ࠶ ࡿ ࠋ
2 㸧 ▷ ᡤ
ձ ࣆ ࣥ ่ ධ 㒊 ࡢ Ύ ₩ ␃ ព ࡋ ࡞ ࠸ ឤ ᰁ ࢆ ㉳ ࡇ ࡋ ࡸ ࡍ ࠸ ࠋ ղ ࣆ ࣥ ࡢ ่ ධ ᪉ ྥ ࣭ ᅛ ᐃ ჾ ࡢ ╔ ᢏ ⾡ ࡀ ᚲ せ ࡛ ࠶ ࡿ ࠋ ճ ༠ ຊ ⓗ ࡛ ࡞ ࠸ ᝈ ⪅ ࡛ ࡣ ᅛ ᐃ ࡀ ⥔ ᣢ ࡛ ࡁ ࡞ ࠸ ࡇ ࡀ ࠶ ࡿ ࠋ մ ╔ 㒊 ࡢ ධ ᾎ ࡀ 㛗 ᮇ ࡛ ࡁ ࡞ ࠸ ࠋ
յ እ ᅛ ᐃ ჾ ࡀ 㧗 ౯ ࡛ ࠶ ࡿ ࠋ
2.1.3.2.4 እ ᅛ ᐃ ἲ ࡢ 㐺 ᛂ
ᚑ ᮶ ࡢ ⒪ ἲ(ෆ ᅛ ᐃ࣭እ ᅛ ᐃ)࡛ ༑ ศ ࡞ ᡂ ⦼ ࡀ ୖ ࡆ ࡽ ࢀ ࡿ 㦵 ᢡ ࡣ 㐺 ᛂ ࡀ ࡞ ࠸ ࠋ ≉ ᐃ ࡢ 㑅 ᢥ ⓗ 㐺 ᛂ ࡀ ࠶ ࡿ ⪃ ࠼ ࡿ ࡁ ࡛ ࠶ ࡿ ࠋ
ձ 㛤 ᨺ ᛶ ⢊ ○ 㦵 ᢡ ղ ⇕ യ ࢆ క ࠺ 㦵 ᢡ ճ ឤ ᰁ ᛶ 㦵 ᢡ ࣭ ഇ 㛵 ⠇
մ 㦵 ㌾ 㒊 Ḟ ᦆ ࡀ ࠶ ࡾ ࠊ ⓶ ᘚ ࡞ ࡢ ᘓ ᡭ ⾡ ࢆ せ ࡍ ࡿ 㦵 ᢡ
յ ⢊ ○ 㒊 ࡢ ࠶ ࡿ ࠺ 㦵 㐲 ➃ 㦵 ᢡ ࡢ ࡈ ࡃ 㦵 㛗 ⥔ ᣢ ࡀ ᡂ ⦼ ᙳ 㡪 ࡢ ࡁ ࠸ 㦵 ᢡ
ն 㦵 ᢡ ࡢ ⒪ ௬ 㦵 ᘏ 㛗 ⾡ ࢆ ᙜ ⾜ ࠺ ࡁ
ࡇ ࢀ ࡽ ࡢ ࠊ ᮲ ௳ ࡼ ࡗ ࡚ እ ᅛ ᐃ ἲ ࢆ 㑅 ࡪ వ ᆅ ࡢ ࠶ ࡿ ࡶ ࡢ ࡣ ࠊ ձ ⭠ 㦵 ࡢ 㦵 ᢡ ࠊ ⬺ ⮻
ղ ⾑ ⟶ ࠊ ⚄ ⤒ ಟ ࢆ ᙜ ⾜ ࠺ ᚲ せ ࡀ ࠶ ࡿ 㦵 ᢡ ճ ከ Ⓨ ᛶ 㦵 ᢡ
մ ෆ ᅛ ᐃ ࡀ ༑ ศ ࡞ 㦵 ᢡ ᑐ ࡍ ࡿ ㏣ ຍ ᅛ ᐃ
2.1.3.2.5 ྜ ే
↓ ไ 㝈 㐺 ᛂ ࡍ ࢀ ࡤ ྜ ే ࡣ ቑ ຍ ࡋ ࡸ ࡍ ࠸ ࠋ 㑅 ᢥ ⓗ ⏝ ࠸ ࠊ 㦵 ᢡ ⒪ ཎ ๎ ྛ እ ᅛ ᐃ ჾ ࡢ ⏝ ᇶ ‽ ࠊ᪉ ἲ ࢆ 㑂 Ᏺ ࡍ ࢀ ࡤ ῶ ࡽ ࡍ ࡇ ࡀ ࡛ ࡁ ࡿ ࠋ
እ ᅛ ᐃ ἲ ࢆ ⾜ ࠺ ࡁ ࡣ ௨ ୗ ࡢ ྜ ే ࡀ Ⓨ ⏕ ࡋ ࡸ ࡍ ࠸ ࡇ ␃ ព ࡋ ࡞ ࡅ
ࢀ ࡤ ࡞ ࡽ ࡞ ࠸ ࠋ
ձ ࣆ ࣥ ࡢ ឤ ᰁ ࡣ ࡶ ࡗ ࡶ ከ ࠸ ྜ ే ࡛ ࠶ ࡿ ࠋ
18
ղ ⚄ ⤒ ࠊ ⾑ ⟶ യ ᐖɆɆࣆ ࣥ ่ ධ 㒊 ࡢ ゎ ๗ Ꮫ ⓗ ᵓ 㐀 ࢆ ᶓ ᩿ 㠃 ࡛ ࡼ ࡃ ⌮ ゎ ࡋ
࡚ ࠾ ࡃ ᚲ せ ࡀ ࠶ ࡿ ࠋᏳ ࡞ ่ ධ 㒊 ᪉ ྥ ࢆ 㑅 ࡪ ࠋୖ ⭎ ࡼ ࡾ ๓ ⭎ ࡅ
࡚ ࠺ 㦵 ⚄ ⤒ ࠊ ๓ ⭎ 㐲 ࡛ ࡢ ࠺ 㦵 ⚄ ⤒ ὸ ᯞ ࠊ ୗ ⭣ ࡛ ࡢ ๓ ⫥ 㦵 ື ⬦ ࠊ
῝ ⭌ 㦵 ⚄ ⤒ ࡀ ࡶ ࡗ ࡶ യ ᐖ ࡀ ከ ࠸ ࠋ
ճ ➽ ⭝ യ ᐖɆɆࣆ ࣥ ࡀ ➽ ⭝ ่ ධ ࡉ ࢀ ࠊ ྍ ື ᛶ ࢆ ไ 㝈 ࡍ ࡿ ࠋ ከ ࡃ ࡣ ࣆ ࣥ
ࢆ ᚋ ᢤ ཤ ࡍ ࡿ ࡇ ࡼ ࡾ ᨵ ၿ ࡍ ࡿ ࡀ ࠊỌ ⥆ ⓗ ⒵ ╔ ࡸ ᩿ ࢆ ṧ ࡍ ࡇ ࡀ ࠶ ࡾ ࠊ ㏣ ຍ ᡭ ⾡ ࢆ せ ࡍ ࡿ ࠋ
մ 㑄 ᘏ ⒪ɆɆ እ ᅛ ᐃ ჾ ࡛ ᅛ ᐃ ࡋ ࠊ 㦵 ᢡ 㒊 ࡢ ච Ⲵ ≧ ែ ࡀ ⥆ ࡃ Ⓨ ⏕ ࡍ
ࡿ ࠋ
2.1.4 㦵 ࡢ ಟ
㦵 ࡣ ✀ ࠎ ࡢ ែ ࡛ ᦆ യ ࡉ ࢀ ࡿ ࡀ ࠊ ࡑ ࡢ ௦ ⾲ ࡋ ࡚ 㦵 ᢡ ࡀ ୖ ࡆ ࡽ ࢀ ࡿ ࠋ 㦵 ᢡ ࡀ ⏕ ࡌ ࡿ ࠊ ึ ᮇ ࡣ ࡢ ⤌ ⧊ ࡢ യ ⒪ ྠ ᵝ ࡞ ಟ ᛂ ࡀ ぢ ࡽ
ࢀ ࡿ ࠋ ࡋ ࡋ ࠊ ⤒ 㐣 ࡶ 㦵 ᢡ 㒊 ࡣ ᪂ ࡓ ࡞ 㦵 ࡀ ᙧ ᡂ ࡉ ࢀ ࠊ ᭱ ⤊ ⓗ
⒕ ⤌ ⧊ ࡛ ࡣ ࡞ ࡃ ࠊ ᮏ ᮶ ࡢ 㦵 ⤌ ⧊ ࡛ ಟ ࡉ ࢀ ࡿ ࡇ ࡀ ≉ ᚩ ࡛ ࠶ ࡿ ࠋ
2.1.4.1 㦵 ᢡ ࡢ ⒵ ཎ ⌮
㦵 ᢡ ࡀ ㉳ ࡇ ࡿ ࠊ ᦆ യ ࡉ ࢀ ࡓ ⓶ 㦵 ࠊ 㦵 㧊 ࠊ 㦵 ⭷ ࠊ ࿘ ᅖ ࡢ ㌾ 㒊 ⤌ ⧊
ࡽ ฟ ⾑ ࡀ ⏕ ࡌ ࠊ ◚ ቯ ࡉ ࢀ ࡚ ቯ Ṛ ࡋ ࡓ ⤌ ⧊ ∦ ࡶ ࠊ 㦵 ᢡ 㒊 ⾑ ⭘ ࢆ ᙧ ᡂ ࡍ ࡿ ࠋ ⾑ ⭘ ࡣ ࣐ ࢡ ࣟ ࣇ ࣮ ࢪ ࡞ ࡢ ⅖ ᛶ ⣽ ⬊ ࡀ ᾐ ₶ ࡋ ࠊ 㦵 ᢡ 㒊
⭘ ⬽ ࠊ ⇕ ឤ ࠊ Ⓨ ㉥ ࡞ ࡢ ⅖ ᛂ ࢆ ᘬ ࡁ ㉳ ࡇ ࡍ ࠋ ୍ ᪉ ࠊ ⾑ ⭘ ࡢ ࿘ ᅖ ࡛ ࡣ ᮍ ศ ࡞ ⣽ ⬊ ࡢ ቑ Ṫ ࡸ ẟ ⣽ ⾑ ⟶ ࡢ ᪂ ⏕ ࡀ ㄆ ࡵ ࡽ ࢀ ࠊ ⾑ ⭘ ࡣ 㝖 ࠎ ⫗ ⱆ ⤌
⧊ ⨨ ࡉ ࢀ ࡚ ࠸ ࡃ ࠋ
ࡑ ࡢ ᚋ ࠊ 㦵 ಟ ≉ ᭷ ࡞ ᪂ ࡓ ࡞ 㦵 ࡢ ᙧ ᡂ ࡀ ጞ ࡲ ࡿ ࠋ 㦵 ᙧ ᡂ ࡣ ࡲ ࡎ 㦵 ᢡ 㒊 ࡽ 㞳 ࢀ ࡓ 㦵 ⭷ ୗ ࡛ ࡳ ࡽ ࢀ ࠊ 㦵 ⭷ ἢ ࡗ ࡚ 㐍 ⾜ ࡋ ࡚ ࠸ ࡃ ࠋ ࡑ ࡢ 㦵 ᙧ ᡂ ࡣ ࠊ ᮍ ศ ࡞ 㛫 ⴥ ⣔ ⣽ ⬊ ࡀ 㦵 ⱆ ⣽ ⬊ ┤ ᥋ ศ ࡋ ࡚ 㦵 ᇶ ㉁ ࢆ ⏘ ⏕ ࡍ ࡿ ࡶ ࡢ ࡛ ࠊࠕ ⭷ ᛶ 㦵 ࠖ ࡤ ࢀ ࡿ ࠋ ୍ ᪉ ࠊ 㦵 ᢡ 㒊 ࡢ ⫗ ⱆ ⤌ ⧊ ࡢ ୰ ࡛ ࡣ ࠊ ᮍ ศ
࡞ ⣽ ⬊ ࡽ ศ ࡋ ࡓ ㌾ 㦵 ⣽ ⬊ ࡀ ㌾ 㦵 ⤌ ⧊ ࢆ ᙧ ᡂ ࡋ ࡚ ࠸ ࡃ ࠋ ㌾ 㦵 ⤌ ⧊ ࡢ
୰ ࡛ ㌾ 㦵 ⣽ ⬊ ࡣ ᚎ ࠎ ⫧ ࡋ ࡚ ࠸ ࡁ ࠊ ᡂ 㛗 ㌾ 㦵 ᯈ ࡛ ࡳ ࡽ ࢀ ࡿ ㌾ 㦵 ෆ 㦵
ྠ ࡌ ᵝ ᘧ ࡛ ㌾ 㦵 ⤌ ⧊ ࡀ 㦵 ⨨ ࡉ ࢀ ࡚ ࠸ ࡃ ࠋ
ࡇ ࡢ ࡼ ࠺ ࡞ 㸰 ✀ 㢮 ࡢ 㦵 㐣 ⛬ ࡢ 㐍 ᒎ ࡼ ࡾ ࠊ 㦵 ᢡ ➃ ࡣ ᪂ ࡓ ᙧ ᡂ ࡉ ࢀ ࡓ 㦵(௬ 㦵)࡛ ⤖ ྜ ࡉ ࢀ ࠊ 㦵 ࡢ 㐃 ⥆ ᛶ ࡀ ᅇ ࡍ ࡿ ࠋ ࡋ ࡋ ࠊ ࡇ ࡢ Ⅼ ࡛ ⏕ ࡌ ࡓ ௬ 㦵 ࡣ ቑ ᯈ ᵓ 㐀 ࢆ ᣢ ࡓ ࡞ ࠸ ⥺ ⥔ ᛶ 㦵 ࡛ ࠶ ࡾ ࠊ ຊ Ꮫ ⓗ ࡣ ⬤ ᙅ ࡞ ⤌ ⧊
࡛ ࠶ ࡿ ࠋ ࡑ ࡢ ᚋ ࠊ 㛗 ᮇ 㛫 ࢃ ࡓ ࡗ ࡚ 㦵 ྾ 㦵 ᙧ ᡂ ࢆ ⧞ ࡾ ㏉ ࡋ ࡞ ࡀ ࡽ ࠊ ௬ 㦵 ࡣ ᒙ ᯈ 㦵 ⨨ ࡉ ࢀ ࠊ ⓶ ㉁ 㦵 ᾏ ⥥ 㦵 ࡽ ࡞ ࡿ 㦵 ᮏ ᮶ ࡢ ⤌ ⧊ ᵓ 㐀
ࢆ ᅇ ࡋ ࡚ ࠸ ࡃ ࠋ ࡇ ࡢ 㐣 ⛬ ࢆ ࣜ ࣔ ࢹ ࣜ ࣥ ࢢ ࠸ ࠺ ࠋ
