A large preclinical animal model to assess ex vivo skin gene therapy applications.

Abstract:

:Because of its easy accessibility, the skin is a very attractive target for gene therapy purposes. To study potential clinical applications in a preclinical setting, appropriate animal models are needed. Pig skin is very similar to human skin, and a variety of human diseases that are potentially amenable to gene therapy applications also occur in pigs. Only a few studies have analyzed the engraftment of transduced keratinocytes (KC) in pigs, however, with limited success. We describe a porcine model in which pig KC were transduced ex vivo with a retroviral vector encoding a marker gene and subsequently grafted onto the autologous host, utilizing a relatively simple grafting technique. Enhanced transduction efficiency was achieved by an optimized transduction protocol including centrifugation of the retroviral vector at a temperature of 32 degrees C. Transduced KC were then seeded onto acellular dermis, forming a stratified epidermis. Grafting was performed by creating full thickness wounds and placing the skin graft onto the muscle fascia, covered by a protective skin flap for several days. Successful engraftment of transduced KC was demonstrated by immunohistochemistry of biopsies taken at different time points, showing transgene expression in 40-50% of grafted KC. After 4 weeks, KC expressing a foreign marker gene was lost, suggesting a transgene-specific immune response in the immunocompetent pigs and highlighting the potential problems for clinical gene therapy studies when transferring new genetic material into a patient. The model presented here may be used to examine applications of skin gene therapy, where retroviral vectors encoding endogenous pig genes will be expressed in the skin.

journal_name

Arch Dermatol Res

authors

Pfützner W,Joari MR,Foster RA,Vogel JC

doi

10.1007/s00403-006-0653-5

keywords:

subject

Has Abstract

pub_date

2006-06-01 00:00:00

pages

16-22

issue

1

eissn

0340-3696

issn

1432-069X

journal_volume

298

pub_type

杂志文章
  • Growth requirements and nitrogen metabolism of Malassezia furfur.

    abstract::Investigations on the nutrient requirements of Malassezia yeasts led to the preparation of a new minimal medium consisting of an amino nitrogen and a lipid source, which only allowed the growth of the species M. furfur. Carbohydrates, electrolytes, vitamins and trace elements were not required. Using the basal medium,...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/s004030050304

    authors: Mayser P,Imkampe A,Winkeler M,Papavassilis C

    更新日期:1998-05-01 00:00:00

  • Cucumis sativus fruit-potential antioxidant, anti-hyaluronidase, and anti-elastase agent.

    abstract::The aim of this study was to screen the antioxidant, anti-hyaluronidase, and anti-elastase activity of the lyophilized juice of Cucumis sativus fruit (CSLJ). The CSLJ was subjected to DPPH and superoxide radical scavenging assay in reference to butylated hydroxytoluene. The hyaluronidase and elastase inhibitory assay ...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/s00403-010-1103-y

    authors: Nema NK,Maity N,Sarkar B,Mukherjee PK

    更新日期:2011-05-01 00:00:00

  • A family study of atopic dermatitis. Clinical and genetic characteristics of 188 patients and 2,151 family members.

    abstract::The history of 188 caucasian patients with atopic dermatitis (AD) and of 2,151 family members has been analyzed. Of the AD patients 48% suffered from respiratory atopy (36% rhinitis, 28% asthma, and 15% both). AD showed by far the earliest onset of all atopic diseases: 50% of our patients had skin lesions before the a...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/BF00493466

    authors: Küster W,Petersen M,Christophers E,Goos M,Sterry W

    更新日期:1990-01-01 00:00:00

  • Modulation of type-IV procollagen and laminin production in A431 human squamous epidermoid carcinoma cells by 12-O-tetradecanoylphorbol-13-acetate (TPA) and epidermal growth factor (EGF).

    abstract::The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) and epidermal growth factor (EGF) on type-IV-procollagen (basement-membrane collagen) and laminin synthesis, turnover, and secretion was studied in human A431 squamous epidermoid carcinoma cells. Type-IV procollagen and laminin were biochemically and immunologic...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/BF00509237

    authors: Panneerselvam M,Sahai A,Salomon DS

    更新日期:1985-01-01 00:00:00

  • Ultrastructure of cultured mouse S91 melanoma cells with special emphasis on viral particles.

    abstract::Mouse S91 melanoma cells which grow as a monolayer in culture were studied by transmission and scanning electron microscopy after fixation in situ. The cells were spindle-shaped and tended to grow in dense colonies. Melanosomes at all stages of melanization (stages I-IV) were observed. Other cell organelles reflected ...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/BF00431064

    authors: Lauharanta J

    更新日期:1989-01-01 00:00:00

  • Association of haptoglobin phenotypes with the development of Kaposi's sarcoma in HIV patients.

    abstract::Kaposi's sarcoma (KS) is a rare cutaneous tumor caused by human herpes virus-8 (HHV-8) infection that preferentially develops in case of severe immunosuppression, such as in HIV/AIDS disease. Haptoglobin (Hp), a polymorphic multifunctional plasma protein, exerts several immunomodulatory effects and is characterized by...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/s00403-011-1161-9

    authors: Speeckaert R,Colebunders B,Boelaert JR,Brochez L,Van Acker J,Van Wanzeele F,Hemmer R,Speeckaert MM,Verhofstede C,De Buyzere M,Arendt V,Plum J,Delanghe JR

    更新日期:2011-12-01 00:00:00

  • Ultrastructure of skin from Refsum disease with emphasis on epidermal lamellar bodies and stratum corneum barrier lipid organization.

    abstract::Classic Refsum disease (RD) is a rare, autosomal recessively-inherited disorder of peroxisome metabolism due to a defect in the initial step in the alpha oxidation of phytanic acid (PA), a C16 saturated fatty acid with four methyl side groups, which accumulates in plasma and lipid enriched tissues (please see van den ...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/s00403-014-1478-2

    authors: Menon GK,Orsó E,Aslanidis C,Crumrine D,Schmitz G,Elias PM

    更新日期:2014-10-01 00:00:00

  • Pathogenesis of lupus dermatoses in autoimmune mice. XIX. Attempts to induce subepidermal immunoglobulin deposition in MRL/Mp- +/+ mice.

    abstract::The deposition of immunoglobulin (Ig) at the dermo-epidermal junction (DEJ) of the skin, frequently observed in autoimmune mouse strains, is similar to that seen in patients with systemic lupus erythematosus (SLE). MRL/Mp-lpr/lpr (MRL/lpr) mice have an autosomal recessive mutant gene, lpr, which produces massive T-cel...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/BF00370818

    authors: Furukawa F,Ohshio G,Imamura S

    更新日期:1993-01-01 00:00:00

  • Strategies to reduce mortality from cutaneous malignant melanoma.

    abstract::The incidence of cutaneous malignant melanoma continues to rise. Strategies to reduce mortality in this situation include improving therapy, encouraging earlier diagnosis, and promoting prevention. New developments such as epiluminescence, sentinel node biopsy, arterial limb perfusion and the use of vaccines are discu...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章,评审

    doi:10.1007/BF00370712

    authors: MacKie RM

    更新日期:1994-01-01 00:00:00

  • Estrone- and dehydroepiandrosterone-sulfatase activities in human female epidermis.

    abstract::Estrone (E1)-sulfatase and dehydroepiandrosterone (DHEA)-sulfatase activities were studied in human female epidermis. Skin specimens were obtained by abdominal or plantar biopsies. The apparent Michaelis-Menten constants for E1 and DHEA sulfatases were 35.2 microM and 8.7 microM, respectively. A substrate inhibition w...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/BF00404316

    authors: Prost O,Nicollier M,Laurent R,Adessi GL

    更新日期:1985-01-01 00:00:00

  • Plasma cluster ions decrease the antigenicity of mite allergens and suppress atopic dermatitis in NC/Nga mice.

    abstract::Mite antigens play important roles in the pathogenesis of atopic dermatitis (AD). We recently developed a novel air cleaner (KC-850U) using charged plasma cluster ions to eliminate a variety of allergens from house environments. The present work demonstrates the ability of KC-850U to decrease the symptoms of AD induce...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/s00403-010-1095-7

    authors: Hiramoto K,Orita K,Yamate Y,Sato EF,Okano H,Nishikawa K,Inoue M

    更新日期:2011-07-01 00:00:00

  • Ultrastructural localization of keratin and alpha-L-fucose in human eccrine sweat glands.

    abstract::Human eccrine sweat glands were embedded in Lowicryl K4M. Cytokeratin proteins and blood group H antigen were localized by applying a postembedding immunogold method using a monoclonal antikeratin antibody and the lectin Ulex europaeus I. The antikeratin antibody labeled intermediate filaments in the secretory coil an...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/BF00505639

    authors: Metzler G,Schaumburg-Lever G,Liebig K

    更新日期:1990-01-01 00:00:00

  • Adhesion of neutrophils to epidermal cells: prerequisites for and blocking by anti-CD11b antibodies.

    abstract::Immigration of neutrophils into the epidermis is a hallmark of several so-called neutrophilic dermatoses. In this study we used a frozen section adhesion assay to study the impact of different activation procedures as well as of CD11 integrins on cell-cell adhesion between neutrophils and epidermal cells. Serial secti...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/s004030050263

    authors: von den Driesch P,Weller M,Wörl P

    更新日期:1997-11-01 00:00:00

  • Effects of metronidazole and tinidazole ointments on models for inflammatory dermatitis in mice.

    abstract::We investigated the effects of 1-4% ointments of metronidazole and tinidazole (derivatives of nitroimidazole) on models of inflammatory dermatitis evoked by antigen, hapten and monoclonal anti-dinitrophenol (DNP) IgE antibody in mice. Metronidazole and tinidazole ointments (1) suppressed the late-phase reaction (LPR) ...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/s00403-002-0381-4

    authors: Nishimuta K,Ito Y

    更新日期:2003-03-01 00:00:00

  • [Physical bases of blister formation. II. A study of the total osmotic pressure in the blister fluid of suction blisters and of "naturally" occurring blisters as well as in the serum].

    abstract::Total osmotic pressure does not differ significantly in suction blister fluid or in serum of healthy persons from blister fluid, suction blister fluid or serum of patients with dermatitis herpetiformis, bullous contact dermatitis and pemphigus vulgaris. The average values reach about 293 mOsmol/kg. This results from d...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:

    authors: Bork K

    更新日期:1978-01-01 00:00:00

  • The development of manifest psoriatic lesions is linked with the invasion of CD8 + T cells and CD11c + macrophages into the epidermis.

    abstract::Koebner response was studied in 35 psoriatic patients. Two punch biopsies per patient were taken from non-lesional psoriatic skin before, and 6 h, 2 days, 7 days, 14 days and 21 days after, tape stripping. Alterations in the numbers of CD1+ Langerhans cells, CD4+ and CD8+ T cells and CD11c+ macrophages were mapped mor...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/BF00372065

    authors: Paukkonen K,Naukkarinen A,Horsmanheimo M

    更新日期:1992-01-01 00:00:00

  • Studies of cellular mediated immunity in malignant melanoma patients by Leukocyte Adherence Inhibition Test.

    abstract::Sixteen malignant melanoma patients with different levels of tumor progression, two patients with melanoma in situ (Clark 10 two bronchogenic carcinoma patients and nine healthy controls were tested by means of the leukocyte adherence inhibition (LAI) test to assess the function of their cellular mediated immunity. Bl...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/BF00403801

    authors: Müller S,Ernst TM

    更新日期:1980-01-01 00:00:00

  • Pathophysiology of cutaneous inflammation.

    abstract::For the better part of the past century, dermatologists have regarded the skin primarily as a large protective coat. Epidermal keratinocytes were highlighted for their production of keratins and lipids, which contributed to the structural integrity and barrier formation of skin. This "saran-wrap" perspective of skin m...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章,评审

    doi:10.1007/BF00638233

    authors: Nickoloff BJ

    更新日期:1992-01-01 00:00:00

  • Cocarcinogenic and tumor-promoting capabilities of anthralin.

    abstract::Numerous chemicals to which humans are exposed either therapeutically or as a result of living in an industrial environment constitute a potential threat as carcinogens, mutagens, and/or tumor promoters and cocarcinogens. Anthralin, and antipsoriatic agent, acts as a tumor promoter for Balb/c-3T3 mouse embryo cell cul...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/BF00429985

    authors: Baturay NZ,Trombetta LD

    更新日期:1988-01-01 00:00:00

  • Hydroperoxides in oxidized d-limonene identified as potent contact allergens.

    abstract::Hydroperoxides of d-limonene were shown to be potent contact allergens when studied in guinea-pigs. Limonene-2-hydroperoxide (2-hydroperoxy-p-mentha-6,8-diene, a mixture of trans and cis isomers) was synthesized for the first time. The ratio between the trans and cis forms was 3:1. These two hydroperoxides were identi...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/BF00370734

    authors: Karlberg AT,Shao LP,Nilsson U,Gäfvert E,Nilsson JL

    更新日期:1994-01-01 00:00:00

  • Alterations in leukocyte aryl hydrocarbon hydroxylase activity associated with treatment and age in psoriasis patients and healthy individuals.

    abstract::We have examined the relationship between topical psoriasis treatment and the activity of the mixed function oxidase, aryl hydrocarbon hydroxylase (AHH), in peripheral blood monocytes and lymphocytes from 20 patients with psoriasis. These data were compared to monocyte and lymphocyte AHH activity measured in 20 normal...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/BF00511066

    authors: Kraemer KH,Robinson RC,Tarone RE,Protic-Sabljic M,Gelboin HV

    更新日期:1984-01-01 00:00:00

  • Distribution and potential biologic function of the thrombin receptor PAR-1 on human keratinocytes.

    abstract::Thrombin has recently been shown not only to exert procoagulant activities, but also to induce mitogenic responses of different cell types involved in wound healing via binding to and cleavage of the thrombin receptor. In order to further explore these aspects of thrombin function, human keratinocytes (HaCaT cell line...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/s004030000168

    authors: Algermissen B,Sitzmann J,Nürnberg W,Laubscher JC,Henz BM,Bauer F

    更新日期:2000-10-01 00:00:00

  • Association of FCER1A genetic polymorphisms with risk for chronic spontaneous urticaria and efficacy of nonsedating H1-antihistamines in Chinese patients.

    abstract::Antihistamines are the first-line treatment for chronic urticaria (CU). However, some CU patients are relatively refractory to antihistamines. The mechanism underlying the interindividual variation is still unknown. The α-chain of the high-affinity IgE receptor is crucial to the IgE-mediated allergic response. The pre...

    journal_title:Archives of dermatological research

    pub_type: 临床试验,杂志文章

    doi:10.1007/s00403-014-1525-z

    authors: Guo A,Zhu W,Zhang C,Wen S,Chen X,Chen M,Zhang J,Su J,Chen W,Zhao Y,Yan S,He Y,Liu Z,Zhou H,Chen X,Li J

    更新日期:2015-03-01 00:00:00

  • Existence of a lipid gradient in the upper stratum corneum and its possible biological significance.

    abstract::The internal stratum corneum lipid composition was investigated in relation to depth in vivo in healthy human volunteers by extraction following one, three or five strippings. Automated multiple development high-performance thin-layer chromatography (AMD-HPTLC) and gas chromatography (GC) followed by normalized princi...

    journal_title:Archives of dermatological research

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1007/s004030050158

    authors: Bonté F,Saunois A,Pinguet P,Meybeck A

    更新日期:1997-01-01 00:00:00

  • Streptococcus sanguinis and the sera of patients with Behçet's disease stimulate membrane expression of α-enolase in human dermal microvascular endothelial cells.

    abstract::The glycolytic enzyme α-enolase is a plasminogen-binding protein that is generally found in the cytosolic compartment. However, α-enolase can also be expressed on cell surfaces following an inflammatory stimulus via an unknown mechanism. We investigated the effects of Streptococcus sanguinis (S. sanguinis) and the ser...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/s00403-012-1298-1

    authors: Cho S,Zheng Z,Cho SB,Choi MJ,Lee KH,Bang D

    更新日期:2013-04-01 00:00:00

  • In vitro activation of immune lymph node cell proliferation by photohapten-modified cells in murine contact photosensitivity.

    abstract::Painting of 3,3',4',5-tetrachlorosalicylanilide (TCSA) plus ultraviolet A (UVA) irradiation to the same site induces contact photosensitivity (CPS), but at the same time results in death of the photohapten-modified cells. Using an in vitro immune lymph node cell (LNC) proliferation system, we investigated the mechanis...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/BF00372063

    authors: Tokura Y,Satoh T,Yamada M,Takigawa M

    更新日期:1991-01-01 00:00:00

  • Detection of fumarate-glutathione adducts in the portal vein blood of rats: evidence for rapid dimethylfumarate metabolism.

    abstract::Dimethylfumarate (DMF), the essential ingredient of the drug product Fumaderm®, is used to treat psoriasis with a recognized favorable long-term safety profile. Interestingly, the mode of action and the pharmacokinetics of DMF in psoriasis or multiple sclerosis are not fully explored. It is known that DMF as an α,β-un...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/s00403-013-1332-y

    authors: Dibbert S,Clement B,Skak-Nielsen T,Mrowietz U,Rostami-Yazdi M

    更新日期:2013-07-01 00:00:00

  • Palmitate induces COX-2 expression via the sphingolipid pathway-mediated activation of NF-κB, p38, and ERK in human dermal fibroblasts.

    abstract::It has been suggested that free fatty acids (FFA) such as palmitate, which are secreted from enlarged adipocytes in the subcutaneous fat of obese subjects, serve as a link between obesity and altered skin functions. Cyclooxygenease-2 (COX-2) and prostanoids participate in the induction of impaired dermal function. In ...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/s00403-013-1434-6

    authors: Oh E,Yun M,Kim SK,Seo G,Bae JS,Joo K,Chae GT,Lee SB

    更新日期:2014-05-01 00:00:00

  • Immunohistochemical study of Toll-like receptors 1 and 2 expression in cutaneous lichen planus lesions.

    abstract::Lichen planus (LP) is a chronic inflammatory, T cell-mediated autoimmune skin disease. Innate immunity could explain the interplay between environmental triggers and the autoimmune cascade leading to disease development. Toll-like receptors (TLRs) are important components of the innate immune system, with no previous ...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/s00403-012-1267-8

    authors: Salem SA,Abu-Zeid RM,Nada OH

    更新日期:2013-03-01 00:00:00

  • Anti-tumor effect of PDT using Photofrin in a mouse angiosarcoma model.

    abstract::Angiosarcoma, a malignant tumor of vascular endothelial cell origin, is a lethal disease for which complete cure is rarely seen. The objective of this study was to determine the efficiency of photodynamic therapy (PDT) as a new treatment for angiosarcoma. PDT (630 nm, 25 J/cm2) using Photofrin for a mouse angiosarcoma...

    journal_title:Archives of dermatological research

    pub_type: 杂志文章

    doi:10.1007/s00403-007-0820-3

    authors: Jin I,Yuji M,Yoshinori N,Makoto K,Mikio M

    更新日期:2008-04-01 00:00:00