营养不良型大疱表皮松解症的治疗研究进展
|
摘要
营养不良型大疱表皮松解症(dystrophic epidermolysis bullosa,DEB)是一种罕见的遗传性疾病,它是一类由于Ⅶ型胶原基因突变或缺失所引起的机械性大疱性疾病,其特征是皮肤水疱及瘢痕的形成,慢性、难以愈合的创伤。根据遗传方式可分为显性遗传营养不良型大疱表皮松解症(dominant dystrophic epidermolysis bullosa,DDEB)和隐性遗传营养不良型大疱表皮松解症(recessive dystrophic epidermolysis bullosa,RDEB)。近年来随着DEB遗传基因、分子发病机制及VII型胶原的结构、功能等方面的研究,DEB的治疗有了很多新的研究成果,有的已经进行临床前试验及临床试验。该文对DEB目前的治疗方法及其新进展进行概述。
Dystrophic epidermolysis bullosa is a rare genetic disease, which is also a kind of mechanical bullous disease caused by the human body type VII collagen gene mutation or loss, characterized by skin blisters and scar formation, chronic and diffi cult to heal wounds. According to the genetic type, the disease can be divided into dominant dystrophic epidermolysis bullosa and recessive dystrophic epidermolysis bullosa. In recent years, with the development of the study of DEB genetic and molecular pathogenesis, structure and function of type VII collagen, DEB treatment has gained a lot of new research results, some of which have carried out preclinical tests and clinical trials. In this paper, present treatment methods and new progress of DEB are summarized.
Dystrophic epidermolysis bullosa is a rare genetic disease, which is also a kind of mechanical bullous disease caused by the human body type VII collagen gene mutation or loss, characterized by skin blisters and scar formation, chronic and diffi cult to heal wounds. According to the genetic type, the disease can be divided into dominant dystrophic epidermolysis bullosa and recessive dystrophic epidermolysis bullosa. In recent years, with the development of the study of DEB genetic and molecular pathogenesis, structure and function of type VII collagen, DEB treatment has gained a lot of new research results, some of which have carried out preclinical tests and clinical trials. In this paper, present treatment methods and new progress of DEB are summarized.
引文
[1]Shinkuma S.Dystrophic epidermolusis[J].Clin Cosmet Investig Dermatol,2015,8:275-284.
[2]Soro L,Bartus C,Purcell S.Recessive dystrophic epidermolysis bullosa:a review of disease pathogenesis and update on future therapies[J].J Clin Aesthet Dermatol,2015,8(5):41-46.
[3]赵辩.中国临床皮肤病学[M].1版.南京:江苏科学技术出版社,2009:1243-1247.
[4]Sari E,Eryilmaz T,Tetik G,et al.Suprathel(®)-assisted surgical treatment of the hand in a dystrophic epidermolysis bullosa patient[J].Int Wound J,2014,11(5):472-475.
[5]Gonzalez ME.Evaluation and treatment of the newborn with epidermolysis bullosa[J].Semin Perinatol,2013,37(1):32-39.
[6]Kirkorian AY,Weitz NA,Tlougan B,et al.Evaluation of wound care options in patients with recessive dystrophic epidermolysis bullosa:a costly necessity[J].Pediatric Dermatol,2014,31(1):33-37.
[7]Haynes L.Nutrition for children with epidermolysis bullosa[J].Dermatol Clin,2010,28(2):289-301.
[8]Shinkuma S,Sawamura D,Fujita Y,et al.Long-term follow-up of cultured epidermal autograft in a patient with recessive dystrophic epidermolysis bullosa[J].Acta Derm Venereol,2014,94(1):98-99.
[9]Hasegawa T,Suga Y,Mizoguchi M,et a1.Clinical trial of alloge-neic cultured dermal substitute for the treatment of intractable skin ulcers in 3 patients with recessive dystrophic epidermolysis bullosa[J].J AM Acad Dermatol,2004,50(5):803-804.
[10]Chino T,Tamai K,Yamazaki T,et a1.Bone marrow cell transfer into fetal circulation can ameliorate genelic skin diseases by providing fibroblasts to the skin and inducing immune to Ierance[J].Am J Patho I,2008,173(3):803-814.
[11]Wagner JE,Ishida-Yamamoto A,Mc Grath JA,et al.Bone marrow transplantation for recessive dystrophic epidermolysis bullosa[J].N Engl J Med,2010,363(7):629-639.
[12]Tolar J,Wagner JE.Allogeneic blood and bone marrow cells for the treatment of severe epidermolysis bullosa:repair of the extracellular matrix[J].Lancet,2013,382(9899):1214-1223.
[13]Wood Iey DT,Krueger GG,Jorgensen CM,et al.Normal and genecorrected dystrophic epidermolysis bullosa fibroblasts alone can produce typeⅦcollagen at the basement membrane zone[J].J Invest Dermal,2003,121(5):1021-1028.
[14]Goto M,Sawamura D,Ito K,et al.Fibroblasts show more potential as target cells than keratinocytes in COL7A1 gene therapy of dystrophic epidermolysis bullosa[J].J Invest Dermatol,2006,126(4):766-772.
[15]Woodley DT,Remington J,Huang Y,et al.Intravenously injected human fibroblasts home to skin wounds,deliver typeⅦcollagen,and promote wound healing[J].Mol Ther,2007,15(3):628-635.
[16]Kern JS,Loeckermann S,Fritsch A,et al.Mechanisms of fibroblast cell therapy for dystrophic epidermolysis bullosa:high stability of collagenⅦfavors long-term skin integrity[J].Mol Ther,2010,17(9):1605-1615.
[17]Wong T,Gammon L,Liu L,et al.Potential of fibroblast cell therapy for recessive dystrophic epidermolysis bullosa[J].J Invest Dermatol,2008,128(9):2179-2189.
[18]Nagy N,Almaani N,Tanaka A,et al.HB-EGF induces COL7A1expression in keratinocytes and fibroblasts:possible mechanism underlying allogeneic fibroblast therapy in recessive dystrophic epidermolysis bullosa[J].J Invest Dermatol,2011,131(8):1771-1774.
[19]Hsu CK,Wang SP,Lee JY,et al.Treatment of hereditary epidermolysis bullosa:updates and future prospects[J].Am J Clin Dermatol,2014,15(1):1-6.
[20]Umegaki-Arao N,Pasmooij AM,Itoh M,et al.Induced pluripotent stem cells from human revertant keratinocytes for the treatment of epidermolysis bullosa[J].Sci Transl Med,2014,6(264):164-264.
[21]Tolar J,Xia L,Riddle MJ,et al.Induced pluripotent stem cells from individuals with recessive dystrophic epidermolysis bullosa[J].J Invest Dermatol,2011,131(4):848-856.
[22]Woodley DT,Keene DR,Atha T,et al.Injection of recombinant human typeⅦcollagen restores collagen function in dystrophic epidermolysis bullosa[J].Nat Med,2004,10(7):693-695.
[23]Wang X,Ghasri P,Amir M,et al.Topical application of recombinant typeⅦcollagen incorporates into the dermal-epidermal junction and promotes wound closure[J].Mol Ther,2013,21(7):1335-1344.
[24]Woodley DT,Wang X,Amir M,et al.Intravenously injected recombinant human type VII collagen homes to skin wounds and restores skin integrity of dystrophic epidermolysis bullosa[J].J Invest Dermatol,2013,133(7):1910-1913.
[25]Hsu CK,Wang SP,Lee JY,et al.Treatment of hereditary epidermolysis bullosa:updates and future prospects[J].Am J Clin Dermatol,2014,15(5):1-6.
[26]Matthias Titeux,Valérie Pendaries,Maria A Zanta-Boussif,etal.Sin Retroviral vectors expressing COL7A1 under human promoters for ex vivogene therapy of recessive dystrophic epidermolysis bullosa[J].Mol Ther,2010,18(8):1509-1518.
[27]Ortiz-Urda S,Lin Q,Green CL,et al.Injection of genetically engineered fibroblasts corrects regeneraled human epiderm Olysis bullosa skin tissue[J].J CIin invest,2003,111(2):251-255.
[28]Chen M,Kasahara N,Keene DR,et a1.Restoration of typeⅦcollagen expression and function in dystrophic epidermolysis bullosa[J].Nat Genet,2002,32(4):670-675.
[2]Soro L,Bartus C,Purcell S.Recessive dystrophic epidermolysis bullosa:a review of disease pathogenesis and update on future therapies[J].J Clin Aesthet Dermatol,2015,8(5):41-46.
[3]赵辩.中国临床皮肤病学[M].1版.南京:江苏科学技术出版社,2009:1243-1247.
[4]Sari E,Eryilmaz T,Tetik G,et al.Suprathel(®)-assisted surgical treatment of the hand in a dystrophic epidermolysis bullosa patient[J].Int Wound J,2014,11(5):472-475.
[5]Gonzalez ME.Evaluation and treatment of the newborn with epidermolysis bullosa[J].Semin Perinatol,2013,37(1):32-39.
[6]Kirkorian AY,Weitz NA,Tlougan B,et al.Evaluation of wound care options in patients with recessive dystrophic epidermolysis bullosa:a costly necessity[J].Pediatric Dermatol,2014,31(1):33-37.
[7]Haynes L.Nutrition for children with epidermolysis bullosa[J].Dermatol Clin,2010,28(2):289-301.
[8]Shinkuma S,Sawamura D,Fujita Y,et al.Long-term follow-up of cultured epidermal autograft in a patient with recessive dystrophic epidermolysis bullosa[J].Acta Derm Venereol,2014,94(1):98-99.
[9]Hasegawa T,Suga Y,Mizoguchi M,et a1.Clinical trial of alloge-neic cultured dermal substitute for the treatment of intractable skin ulcers in 3 patients with recessive dystrophic epidermolysis bullosa[J].J AM Acad Dermatol,2004,50(5):803-804.
[10]Chino T,Tamai K,Yamazaki T,et a1.Bone marrow cell transfer into fetal circulation can ameliorate genelic skin diseases by providing fibroblasts to the skin and inducing immune to Ierance[J].Am J Patho I,2008,173(3):803-814.
[11]Wagner JE,Ishida-Yamamoto A,Mc Grath JA,et al.Bone marrow transplantation for recessive dystrophic epidermolysis bullosa[J].N Engl J Med,2010,363(7):629-639.
[12]Tolar J,Wagner JE.Allogeneic blood and bone marrow cells for the treatment of severe epidermolysis bullosa:repair of the extracellular matrix[J].Lancet,2013,382(9899):1214-1223.
[13]Wood Iey DT,Krueger GG,Jorgensen CM,et al.Normal and genecorrected dystrophic epidermolysis bullosa fibroblasts alone can produce typeⅦcollagen at the basement membrane zone[J].J Invest Dermal,2003,121(5):1021-1028.
[14]Goto M,Sawamura D,Ito K,et al.Fibroblasts show more potential as target cells than keratinocytes in COL7A1 gene therapy of dystrophic epidermolysis bullosa[J].J Invest Dermatol,2006,126(4):766-772.
[15]Woodley DT,Remington J,Huang Y,et al.Intravenously injected human fibroblasts home to skin wounds,deliver typeⅦcollagen,and promote wound healing[J].Mol Ther,2007,15(3):628-635.
[16]Kern JS,Loeckermann S,Fritsch A,et al.Mechanisms of fibroblast cell therapy for dystrophic epidermolysis bullosa:high stability of collagenⅦfavors long-term skin integrity[J].Mol Ther,2010,17(9):1605-1615.
[17]Wong T,Gammon L,Liu L,et al.Potential of fibroblast cell therapy for recessive dystrophic epidermolysis bullosa[J].J Invest Dermatol,2008,128(9):2179-2189.
[18]Nagy N,Almaani N,Tanaka A,et al.HB-EGF induces COL7A1expression in keratinocytes and fibroblasts:possible mechanism underlying allogeneic fibroblast therapy in recessive dystrophic epidermolysis bullosa[J].J Invest Dermatol,2011,131(8):1771-1774.
[19]Hsu CK,Wang SP,Lee JY,et al.Treatment of hereditary epidermolysis bullosa:updates and future prospects[J].Am J Clin Dermatol,2014,15(1):1-6.
[20]Umegaki-Arao N,Pasmooij AM,Itoh M,et al.Induced pluripotent stem cells from human revertant keratinocytes for the treatment of epidermolysis bullosa[J].Sci Transl Med,2014,6(264):164-264.
[21]Tolar J,Xia L,Riddle MJ,et al.Induced pluripotent stem cells from individuals with recessive dystrophic epidermolysis bullosa[J].J Invest Dermatol,2011,131(4):848-856.
[22]Woodley DT,Keene DR,Atha T,et al.Injection of recombinant human typeⅦcollagen restores collagen function in dystrophic epidermolysis bullosa[J].Nat Med,2004,10(7):693-695.
[23]Wang X,Ghasri P,Amir M,et al.Topical application of recombinant typeⅦcollagen incorporates into the dermal-epidermal junction and promotes wound closure[J].Mol Ther,2013,21(7):1335-1344.
[24]Woodley DT,Wang X,Amir M,et al.Intravenously injected recombinant human type VII collagen homes to skin wounds and restores skin integrity of dystrophic epidermolysis bullosa[J].J Invest Dermatol,2013,133(7):1910-1913.
[25]Hsu CK,Wang SP,Lee JY,et al.Treatment of hereditary epidermolysis bullosa:updates and future prospects[J].Am J Clin Dermatol,2014,15(5):1-6.
[26]Matthias Titeux,Valérie Pendaries,Maria A Zanta-Boussif,etal.Sin Retroviral vectors expressing COL7A1 under human promoters for ex vivogene therapy of recessive dystrophic epidermolysis bullosa[J].Mol Ther,2010,18(8):1509-1518.
[27]Ortiz-Urda S,Lin Q,Green CL,et al.Injection of genetically engineered fibroblasts corrects regeneraled human epiderm Olysis bullosa skin tissue[J].J CIin invest,2003,111(2):251-255.
[28]Chen M,Kasahara N,Keene DR,et a1.Restoration of typeⅦcollagen expression and function in dystrophic epidermolysis bullosa[J].Nat Genet,2002,32(4):670-675.