骨髄由来表皮細胞の遊走機序の解明ならびに臨床応用

• Project/Area Number: 18689027
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Dermatology
• Research Institution: Hokkaido University
• Principal Investigator: 阿部 理一郎 Hokkaido University, 北海道大学病院, 講師 (60344511)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥28,730,000 (Direct Cost: ¥22,100,000、Indirect Cost: ¥6,630,000); Fiscal Year 2007: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000); Fiscal Year 2006: ¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
• Keywords: 再生医療

Research Abstract

これまで再生医学領域の研究により、種々の体細胞成分が骨髄幹細胞から分化可能であることが明らかとなった。本研究の目的は、表皮水疱症(先天性基底膜構造タンパク欠損症)に対して、同種骨髄移植を行い、ドナー骨髄由来表皮細胞から欠損基底膜タンパクを産生させることにより、治癒させることである。
本研究課題において、1)骨髄細胞からの表皮細胞への分化の同定、2)骨髄細胞由来表皮細胞の表皮への効率的遊走機序の検討、3)骨髄細胞由来表皮細胞に特異的なケモカインを用いた創傷治癒への関与の検討、4)骨髄由来表皮細胞の表皮細胞特異的機能の確認、5)表皮構成タンパク欠損マウスにおける骨髄幹細胞由来表皮細胞の分化の同定、を行った。
それぞれにおいて、1)In vitroにおいて骨髄細胞に種々の液性因子を添加することで、表皮細胞分化が促進されるか検討したところBMP-4など数種の候補が同定できた。2)骨髄由来表皮細胞遊走促進させる特異的ケモカインを同定した。3)同定したケモカイン局所投与にて創傷治癒は有意に促進した。4)ヒト基底膜タンパク発現マウスから正常マウスへの骨髄移植で、移植されたマウスの創傷部に、ヒト基底膜の発現を認めた。5)基底膜タンパク欠損マウスに正常マウスから骨髄移植を行ったところ、欠損マウス皮膚創傷部に、正常骨髄由来のタンパクの発現を認めた。
以上のように当初予定した研究計画をほぼ施行でき、かつ結果も得られた。

Research Products

• [Journal Article] Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type. (2008)
  • Author(s): Sasaki M
  • Journal Title: J Immunol 180 Pages: 2581-2587
  • Peer Reviewed
• [Journal Article] Macrophage migration inhibitory factor (MIF) in bullous pemphigoid. (2008)
  • Author(s): Asano Y
  • Journal Title: J Dermatol Sci 49 Pages: 95-97
  • Peer Reviewed
• [Journal Article] Interleukin-1beta and macrophage migration inhibitory factor (MIF) in dermal fibroblasts mediate UVA Induced matrix metalloproteinase-lexpression. (2008)
  • Author(s): Honda A
  • Journal Title: J Dermatol Sci 49 Pages: 63-72
  • Peer Reviewed
• [Journal Article] Soluble Fas ligand: is it critical mediator of TEN/SJS? (2008)
  • Author(s): Murata J
  • Journal Title: J Dermatol Sci 49 Pages: 63-72
  • Peer Reviewed
• [Journal Article] Pigment epithelium-derived factor (PEDF) inhibits vascular endothelial growth factor (VEGF)-induced vascular hyperpermeability both in vitro and in vivo. (2007)
  • Author(s): Yamagishi S
  • Journal Title: J Int Med Res 35 Pages: 896-899
  • Peer Reviewed
• [Journal Article] Small diameter porous poly (ε-calprolactone) films enhance adhesion and growth of human cultured epidermal keratinocyte and dermal fibroblast cells. (2007)
  • Author(s): McMillan JR
  • Journal Title: Tissue Eng 13 Pages: 789-798
  • Peer Reviewed
• [Journal Article] Granulomatous arteritis in cutaneous lesions of Churg-Strauss syndrome. (2007)
  • Author(s): Chen KR
  • Journal Title: J Cutan Pathol 34 Pages: 330-337
  • Peer Reviewed
• [Journal Article] Angiogenesis and metastasis inhibitors for the treatment of malignant melanoma. (2007)
  • Author(s): Abe R
  • Journal Title: Mini Rev Med Chem 7 Pages: 649-661
  • Peer Reviewed
• [Journal Article] Small diameter porous poly (ε-calprolactone) films enhance adhesion and growth of human cultured epidermal keratinocyte and dermal fibroblast cells. (2007)
  • Author(s): McMillan JR, Abe R, et al.
  • Journal Title: Tissue Engineering (in press)
• [Journal Article] Granulomatous arteritis in cutaneous lesions of Churg- Strauss syndrome. (2007)
  • Author(s): Chen KR, Abe R, et al.
  • Journal Title: J Cutan Pathol 34 Pages: 330-337
• [Journal Article] Unilateral periorbital oedema due to sarcoid infiltration of the eyelid : an unusual presentation of sarcoidosis with facial nerve palsy and parotid gland enlargement. (2007)
  • Author(s): Yaosaka M, Abe R, et al.
  • Journal Title: Brit J Dermatol (In press)
• [Journal Article] CTACK/CCL27 accelerates skin regeneration via accumulation of bone marrow derived-keratinocytes. (2006)
  • Author(s): Inokuma D, Abe R, et al.
  • Journal Title: Stem Cells 24 Pages: 2810-2816
• [Journal Article] Presence of circulating CCR10+ T-cells and elevated serum CTACK/CCL27 in the early stage of mycosis fungoides. (2006)
  • Author(s): Fujita Y, Abe R, et al.
  • Journal Title: Clin Cancer Res 12 Pages: 2670-2675
• [Journal Article] Protemics and bioinformatics characterization of the biogenesis and function of melanosomes. (2006)
  • Author(s): Chi A, Abe R, et al.
  • Journal Title: J Proteome Res 5 Pages: 3135-3144
• [Journal Article] Increase of macrophage migration inhibitory factor levels in lacrimal fluid of patients with severe atopic dermatitis. (2006)
  • Author(s): Kitaichi N, Abe R, et al.
  • Journal Title: Graefes Arch Clin Exp Ophthalmol 244 Pages: 825-828
  • NAID: 120000964444
• [Journal Article] Two cases of folliculosebaceous cystic hamartoma. (2006)
  • Author(s): Tanimura S, Abe R, et al.
  • Journal Title: Clin Exp Dermatol 31 Pages: 68-70
• [Journal Article] Coexistence of systemic lupus erythematosus and porphyria cutanea tarda-a case successfully improved by avoidance of sun exposure-. (2006)
  • Author(s): Murata J, Abe R, et al.
  • Journal Title: Int J Dermatol 45 Pages: 435-437
  • NAID: 120000961306
• [Journal Article] Improvement of mycosis fungoides during treatment of hepatitis C with peginterferon alfa-2b. (2006)
  • Author(s): Yanagi T, Abe R, et al.
  • Journal Title: Arch Dermatol 142 Pages: 649-649
• [Journal Article] Mycosis fungoides bullosa. (2006)
  • Author(s): Natsuga K, Abe R, et al.
  • Journal Title: Arch Dermatol 142 Pages: 793-795
• [Journal Article] Chain saw granuloma : reaction to the deep implanted chain saw fragment. (2006)
  • Author(s): Osawa R, Abe R, et al.
  • Journal Title: Arch Dermatol 142 Pages: 1079-1080
• [Journal Article] Disseminated subcutaneous nodules alone as manifestations of Churg-Strauss syndrome.
  • Author(s): Abe R
  • Journal Title: Int J Dermatol (In press)
  • Peer Reviewed
• [Remarks]
  • URL: http://www.derm-hokudai.jp/