Clinical Results of an Autologous Engineered Skin

Llames, Sara; García, Eva; García, Verónica; Río, Marcela Del; Larcher, Fernando; Jorcano, José L.; López, Eva; Holguín, Purificación; Miralles, F.; Otero, Jesús María Garagorri; Meana, Álvaro

doi:10.1007/s10561-004-7253-4

Cited by 92 publications

(78 citation statements)

References 18 publications

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“…9,10,29,30 Finally, it is also important to mention that this bioengineered skin equivalent has been widely used for permanent skin regeneration in patients suffering severe skin losses. 7,31 In the present study, we move another step forward by introducing in this well-characterized skin humanized mouse model specific cytokine-producing lymphocytes to model a complex skin disease, such as psoriasis, in which the immune component plays a central role.…”

Section: Discussionmentioning

confidence: 99%

Development of a Bioengineered Skin-Humanized Mouse Model for Psoriasis

Guerrero-Aspizua

García

Murillas

et al. 2010

The American Journal of Pathology

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Over the past few years, whole skin xenotransplantation models that mimic different aspects of psoriasis have become available. However, these models are strongly constrained by the lack of skin donor availability and homogeneity. We present in this study a bioengineering-based skin-humanized mouse model for psoriasis, either in an autologous version using samples derived from psoriatic patients or, more importantly, in an allogeneic context, starting from skin biopsies and blood samples from unrelated healthy donors. After engraftment, the regenerated human skin presents the typical architecture of normal human skin but, in both cases, immunological reconstitution through intradermal injection in the regenerated skin using in vitro-differentiated T1 subpopulations as well as recombinant IL-17 and IL-22 Th17 cytokines, together with removal of the stratum corneum barrier by a mild abrasive treatment, leads to the rapid conversion of the skin into a bona fide psoriatic phenotype. Major hallmarks of psoriasis were confirmed by the evaluation of specific epidermal differentiation and proliferation markers as well as the mesenchymal milieu, including angiogenesis and infiltrate. Our bioengineered skin-based system represents a robust platform to reliably assess the molecular and cellular mechanisms underlying the complex interdependence between epidermal cells and the immune system. The system may also prove suitable to assess preclinical studies that test the efficacy of novel therapeutic treatments and to predict individual patient response to therapy. Psoriasis is a T cell-mediated inflammatory skin disorder, multifactorial in its etiology. It affects about 2% of the worldwide population. There is a wide range of clinical presentations of the disease, but the most common variety is the chronic plaque psoriasis. In many cases the severity of the outcome may have serious (disabling) physical as well as psychological consequences.1 Several transgenic and knockout mouse models of the disease have been developed to date, and they have been proved to be valuable tools to establish the contribution of specific molecules to the pathogenesis of the disease.2,3 However, none of them fully recapitulates the complex pathophysiology of human psoriasis. Moreover, human skin presents major differences with mouse skin, making it more difficult to mimic the human condition.

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Section: Discussionmentioning

confidence: 99%

Development of a Bioengineered Skin-Humanized Mouse Model for Psoriasis

Guerrero-Aspizua

García

Murillas

et al. 2010

The American Journal of Pathology

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“…In fact, only one skin biopsy donation may suffice to generate a big surface of bioengineered skin constructs, enabling in turn the production of a large number of skin-humanized mice. 12 A new skin-humanized mouse model based on the grafting of a skin equivalent, previously used in clinics for permanent skin regeneration in burn patients, 13,14 was recently shown to be a suitable model for the study of physiological processes such as wound healing in a human context. 15,16 Moreover, the platform allows trustworthy and efficient modeling and gene therapy of inherited skin diseases such as different forms of Epidermolysis Bullosa.…”

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confidence: 99%

In Vivo Assessment of Acute UVB Responses in Normal and Xeroderma Pigmentosum (XP-C) Skin-Humanized Mouse Models

García

Llames

García

et al. 2010

The American Journal of Pathology

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In vivo studies of UVB effects on human skin are precluded by ethical and technical arguments on volunteers and inconceivable in cancer-prone patients such as those affected with Xeroderma Pigmentosum (XP). Establishing reliable models to address mechanistic and therapeutic matters thus remains a challenge. Here we have used the skin-humanized mouse system that circumvents most current model constraints. We assessed the UVB radiation effects including the sequential changes after acute exposure with respect to timing, dosage, and the relationship between dose and degree-sort of epidermal alteration. On Caucasian-derived regenerated skins , UVB irradiation (800 J/m 2 ) induced DNA damage (cyclobutane pyrimidine dimers) and p53 expression in exposed keratinocytes. Epidermal disorganization was observed at higher doses. In contrast, in African descent-derived regenerated skins, physiological hyperpigmentation prevented tissue alterations and DNA photolesions. The acute UVB effects seen in Caucasian-derived engrafted skins were also blocked by a physical sunscreen, demonstrating the suitability of the system for photoprotection studies. We also report the establishment of a photosensitive model through the transplantation of XP-C patient cells as part of a bioengineered skin. The inability of XP-C engrafted skin to remove DNA damaged cells was confirmed in vivo. Both the normal and XP-C versions of the skin-humanized mice proved proficient models to assess UVB-mediated DNA repair responses and provide a strong platform to test novel therapeutic strategies.

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“…Thus, fibrin is not only a reservoir of different factors but also provides an appropriate three-dimensional scaffold that promotes the migration, proliferation, and differentiation of cells in the wound bed. 13,16 Similarly, the human dermal fibroblasts in the matrix strongly induce keratinocyte proliferation, making it possible to dispense with the use of coadjuvant mouse cells (a feeder layer).…”

Section: Skin Bioengineering In Clinical Practicementioning

confidence: 99%

“…The autologous version has been used to achieve permanent tissue regeneration in various situations (major burns, necrotizing fasciitis, wound closure following resection of giant nevus, and in graft-versus-host disease). 13,15,18 An allogeneic version has been used in the treatment of chronic ulcers (Fig. 2).…”

Section: Skin Bioengineering In Clinical Practicementioning

confidence: 99%