Investigation of hematopoietic stem cell transplantation for epidermolysis bullosa

• Project/Area Number: 24249062
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Hokkaido University
• Principal Investigator: SHIMIZU Hiroshi 北海道大学, 医学(系)研究科(研究院), 教授 (00146672)
• Co-Investigator(Kenkyū-buntansha): ABE Riichiro 北海道大学, 大学院医学研究科, 准教授 (60344511) ; NISHIE Wataru 北海道大学, 北海道大学病院, 講師 (20443955) ; FUJITA Yasuyuki 北海道大学, 北海道大学病院, 助教 (80374437) ; AKIYAMA Masashi 名古屋大学, 大学院医学系研究科, 教授 (60222551) ; KOJIMA Seiji 名古屋大学, 大学院医学系研究科, 教授 (20313992)
• Co-Investigator(Renkei-kenkyūsha): NAKAMURA Hideki 北海道大学, 大学院医学研究科, 助手 (60435956)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥45,630,000 (Direct Cost: ¥35,100,000、Indirect Cost: ¥10,530,000); Fiscal Year 2014: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2013: ¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000); Fiscal Year 2012: ¥25,870,000 (Direct Cost: ¥19,900,000、Indirect Cost: ¥5,970,000)
• Keywords: 表皮水疱症 / 幹細胞移植 / 細胞療法 / 造血幹細胞移植 / iPS細胞 / 17型コラーゲン

Outline of Final Research Achievements

Epidermolysis bullosa (EB) is a group of genodermatoses that cause blister formations from the congenital abnormality of anchor proteins between the epidermis and the dermis. There have been several strategies for the treatment of EB, and so far, cell therapies are the most promising approach because of the potential of systemic effects. We have proved that stem cell therapies, including bone marrow transplantation, hematopoietic stem cell transplantation, can ameliorate the phenotype and survival prognosis in the junctional EB model mice that lack type XVII collagen (Col17). In this study we explore more efficient approaches of stem cell therapies for EB, including intramedullary transplantation, mesenchymal stromal/stem cell infusion, and investigate factors in association with transdifferentiation from bone marrow-derived stem cells into keratinocytes.

Research Products

• [Journal Article] Skipped exon in COL7A1 determines the clinical phenotypes of dystrophic epidermolysis bullosa. (2015)
  • Author(s): Toyonaga E, Nishie W, Komine M, Murata S, Shinkuma S, Natsuga K, Nakamura H, Ohtsuki M, Shimizu H.
  • Journal Title: British Journal of Dermatology Volume: 172 Issue: 4 Pages: 1141-1144
  • DOI: 10.1111/bjd.13386
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] An annexin A1-FPR1 interaction contributes to necroptosis of keratinocytes in severe cutaneous adverse drug reactions. (2014)
  • Author(s): Saito N, Qiao H, Yanagi T, Shinkuma S, Nishimura K, Suto A, Fujita Y, Suzuki S, Nomura T, Nakamura H, Nagao K, Obuse C, Shimizu H, Abe R.
  • Journal Title: Science Translational Medicine Volume: 6 Issue: 245 Pages: 245-295
  • DOI: 10.1126/scitranslmed.3008227
  • Peer Reviewed / Open Access
• [Journal Article] Long-term follow-up of cultured epidermal autograft in a patient with recessive dystrophic epidermolysis bullosa (2014)
  • Author(s): Shinkuma S, Sawamura D, Fujita Y, Kawasaki H, Nakamura H, Inoie M, Nishie W, Shimizu H
  • Journal Title: Acta Derm Venereol Volume: 94(1) Issue: 1 Pages: 98-99
  • DOI: 10.2340/00015555-1592
  • Peer Reviewed
• [Journal Article] Stevens-Johnson syndrome/toxic epidermal necrolysis mouse model generated by using PBMCs and the skin of patients. (2013)
  • Author(s): Saito N, Yoshioka N, Abe R, Qiao H, Fujita Y, Hoshina D, Suto A, Kase S, Kitaichi N, Ozaki M, Shimizu H.
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 131 Issue: 2 Pages: 434-441
  • DOI: 10.1016/j.jaci.2012.09.014
  • Peer Reviewed
• [Journal Article] Establishment of a novel experimental model of human angiosarcoma and a VEGF-targeting therapeutic experiment. (2013)
  • Author(s): Hoshina D, Abe R, Yoshioka N, Saito N, Hata H, Fujita Y, Aoyagi S, Shimizu H.
  • Journal Title: Journal of Dermatological Science Volume: 70 Issue: 2 Pages: 116-122
  • DOI: 10.1016/j.jdermsci.2013.02.008
  • Peer Reviewed
• [Journal Article] Jacyk、Ken Natsuga、Hideyuki Ujiie、Hideki Nakamura、Masashi Akiyama、Hiroshi Shimizu (2013)
  • Author(s): Satoru Shinkuma、Wataru Nishie、 Witold K
  • Journal Title: A Novel Keratin 5 Mutation in an African Family with Epidermolysis Bullosa Simplex Indicates the Importance of the Amino Acid Located at the Boundary Site Between the H1 and Coil 1A Domains Volume: 印刷中 Issue: 5 Pages: 585-587
  • DOI: 10.2340/00015555-1538
  • Peer Reviewed
• [Journal Article] Conversion from human haematopoietic stem cells to keratinocytes requires keratinocyte secretory factors (2012)
  • Author(s): Fujita Y, Inokuma D, et al.
  • Journal Title: Clinical and Experimental Dermatology Volume: (印刷中) Issue: 6 Pages: 658-664
  • DOI: 10.1111/j.1365-2230.2011.04312.x
  • Peer Reviewed
• [Journal Article] Type VII collagen deficiency causesdefective tooth enamel formation due to poor differentiation of ameloblasts (2012)
  • Author(s): Umemoto H, Akiyama M, Domon T, Nomura T, Shinkuma S, Ito K, Asaka T, Sawamura D, Uitto J, Uo M, Kitagawa Y, Shimizu H
  • Journal Title: Am J Pathol Volume: 181 Issue: 5 Pages: 1659-71
  • DOI: 10.1016/j.ajpath.2012.07.018
  • Peer Reviewed
• [Presentation] RNA recognition motif of LEMD3 as a key player in the pathogenesis of Buschke-Ollendorff syndrome. (2015)
  • Author(s): Takashima S, Fujita Y, Suzuki S, Saito N, Shinkuma S, Nomura T, Shimizu H.
  • Organizer: The 71st Annual Meeting of the Society for Investigative Dermatology
  • Place of Presentation: Atlanta, US
  • Year and Date: 2015-05-06 – 2015-05-09
• [Presentation] Highly prevalent SERPINB7 founder mutation causes pseudodominant inheritance pattern in Nagashima-type palmoplantar keratosis. (2014)
  • Author(s): Mizuno O, Nomura T, Suzuki S, Takeda M, Ohguchi Y, Fujita Y, Nishie W, Sugiura K, Akiyama M, Shimizu H
  • Organizer: The 44th European Society for Dermatological Research (ESDR) Annual Meeting
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2014-09-10 – 2014-09-13
• [Presentation] Epidermolysis bullosa in Japan: from bench to bedside. (2014)
  • Author(s): Fujita Y
  • Organizer: The 37th Kung-Sun Oh Memorial Lecture
  • Place of Presentation: Yonsei University (Seoul, Korea)
  • Year and Date: 2014-08-30
  • Invited
• [Presentation] Novel strategies for the treatment of epidermolysis bullosa. (2013)
  • Author(s): Fujita Y
  • Organizer: The 1st Beijing International Forum of Pediatric Development.
  • Place of Presentation: Beijing International Conference Center (Beijing, China)
  • Invited
• [Presentation] 表皮水疱症の病態と治療 (2012)
  • Author(s): 藤田靖幸
  • Organizer: 第76回日本皮膚科学会東部支部学術大会
  • Place of Presentation: ロイトン札幌（北海道）
  • Invited
• [Presentation] Circulating stem cells and wounded skin in epidermolysis bullosa; possible role of chemokines in the recruitment of cells from bone marrow to skin. (2012)
  • Author(s): Yasuyuki Fujita
  • Organizer: The 37th Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: ロワジールホテル那覇（沖縄県）
  • Invited
• [Presentation] 自家培養表皮移植を行い長期観察した 劣性栄養障害型表皮水疱症の1例 (2012)
  • Author(s): 藤田靖幸
  • Organizer: 第42回日本創傷治癒学会
  • Place of Presentation: かでる２・７（北海道）