Investigation of induced stem cells treatment for epidermolysis bullosa

• Project/Area Number: 25713041
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Dermatology
• Research Institution: Hokkaido University
• Principal Investigator: FUJITA Yasuyuki 北海道大学, 大学病院, 助教 (80374437)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥26,130,000 (Direct Cost: ¥20,100,000、Indirect Cost: ¥6,030,000); Fiscal Year 2014: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000); Fiscal Year 2013: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
• Keywords: 表皮水疱症 / iPS細胞 / 人工多能性幹細胞 / 造血系幹細胞 / 17型コラーゲン / 造血幹細胞移植

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 the possibility of induced pluripotent stem cells (iPSCs) for the treatment of EB, via induction of hematopoietic cell lineages. We preformed iPSCs-derived hematopoietic stem cell transplantation to Col17 knockout / Col17 humanized mice, and some of them showed slight expression of the lacked murine Col17 in the re-epithelized skin injuries.

Research Products

• [Journal Article] MMP13 can be a useful differentiating marker between squamous cell carcinoma and benign hyperkeratotic lesions in recessive dystrophic epidermolysis bullosa. (2015)
  • Author(s): Hata H, Abe R, Suto A, Homma E, Fujita Y, Aoyagi S, Shimizu H.
  • Journal Title: British Journal of Dermatology Volume: 172 Issue: 3 Pages: 769-773
  • DOI: 10.1111/bjd.13302
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Development of bullous pemphigoid during treatment of psoriatic onycho-pachydermo periostitis with ustekinumab. (2015)
  • Author(s): Nakayama C, Fujita Y, Watanabe M, Shimizu H
  • Journal Title: Journal of Dermatology Volume: -
  • Peer Reviewed
• [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] Disturbed balance in three subpopulations of CD4(+)Foxp3(+) regulatory T cells in Stevens-Johnson syndrome and toxic epidermal necrolysis patients. (2013)
  • Author(s): Yoshioka N, Suto A, Abe R, Saito N, Murata J, Hayashi-Ujiie I, Hoshina D, Fujita Y, Shimizu H.
  • Journal Title: Clin Immunol Volume: 148 Issue: 1 Pages: 89-91
  • DOI: 10.1016/j.clim.2013.04.002
  • Peer Reviewed
• [Presentation] GVHD-like manifestation in Thymoma: Thymoma-associated multiorgan autoimmunity. (2015)
  • Author(s): Muramatsu K, Fujita Y, Inokuma D, Tsukinaga I, Ito K, Nishiura Y, Shimizu H
  • Organizer: The 23rd World Congress of Dermatology
  • Place of Presentation: Vancouver Convention Centre (Vancouver, Canada)
  • Year and Date: 2015-06-08 – 2015-06-13
• [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: Hilton Atlanta Hotel (Atlanta, USA)
  • Year and Date: 2015-05-06 – 2015-05-09
• [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): Yasuyuki Fujita
  • Organizer: The 1st Beijing International Forum of Pediatric Development.
  • Place of Presentation: Beijing International Conference Center (Beijing, China)
  • Invited