Multicentre experience in the treatment of burns with autologous and allogenic cultured epithelium, fresh or preserved in a frozen state

Luca, Michele De; Albanese, Enrico; Bondanza, Sergio; Megna, Matteo; Ugozzoli, Luis A.; Molina, Francesco; Cancedda, Ranieri; Santi, P. L.; Bormioli, M; Stella, Maurizio; Magliacani, G.

doi:10.1016/0305-4179(89)90007-7

Cited by 247 publications

(110 citation statements)

References 11 publications

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“…At present, only ex vivo retroviral delivery to autologous keratinocytes followed by skin grafting has thus far led to successful correction of the JEB subtype in the clinical setting (Mavilio et al, 2006). As a main source of type VII collagen-producing cells in vivo (Burgeson, 1993), autologous cultured keratinocytes have been widely used for the permanent coverage of severe fullthickness burns with further indication of the long-term reepithelialization of the grafted sites (De Luca et al, 1989;Pellegrini et al, 1998). Moreover, earlier preclinical studies showed successful correction of the RDEB phenotype using ex vivo gene therapy and keratinocytes modified with either viral (Chen et al, 2002;Gache et al, 2004) or nonviral (OrtizUrda et al, 2002) vectors.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Type VII Collagen Restoration to Human Epidermolysis Bullosa Skin Tissue

et al. 2010

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In spite of advances in the molecular diagnosis of recessive dystrophic epidermolysis bullosa (RDEB), an inherited blistering disease due to a deficiency of type VII collagen at the basement membrane zone (BMZ) of stratified epithelium, current therapy is limited to supportive palliation. Gene delivery has shown promise in short-term experiments; however, its long-term sustainability through multiple turnover cycles in human tissue has awaited confirmation. To characterize approaches for long-term genetic correction, retroviral vectors were constructed containing long terminal repeat-driven full-length and epitope-tagged COL7A1 cDNA and evaluated for durability of type VII collagen expression and function in RDEB skin tissue regenerated on immunedeficient mice. Type VII collagen expression was maintained for 1 year in vivo, or over 12 epidermal turnover cycles, with no abnormalities in skin morphology or self-renewal. Type VII collagen restoration led to correction of RDEB disease features, including reestablishment of anchoring fibrils at the BMZ. This approach confirms durably corrective and noninjurious gene delivery to long-lived epidermal progenitors and provides the foundation for a human clinical trial of ex vivo gene delivery in RDEB.

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Section: Discussionmentioning

confidence: 99%

Long-Term Type VII Collagen Restoration to Human Epidermolysis Bullosa Skin Tissue

et al. 2010

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“…In fact, cultured epidermal are taken as a permanent coverage of wounds, and they are known as an epoch-making treatment for large burns for which an adequate skin replacement is complex to achieve 4,13 . However, usually acute burn patients have to wait for the growth of the epidermis once the epidermal culture requires almost one month.…”

Section: Introductionmentioning

confidence: 99%

“…In the literature, several authors have described the cultured epidermal allografts for freezing, expanding its availability and making your employment as a viable clinical alternative 3,5,6,13 . Thus, the cryopreservation of cultured epithelium has been a constant search topic in many centers worldwide 3,5,[13][14][15] .…”

Section: Introductionmentioning

confidence: 99%

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An outcome analysis and long-term viability of cryopreserved cultured epidermal allografts: assessment of the conservation of transplantable human skin allografts

et al. 2013

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PURPOSE:To assess the viability of cultured epithelium and preserved by freezing for periods varying from one month to one year. METHODS:Samples of cultured epithelium were incubated in cryoprotectant medium (Group A), packed in aluminum envelopes and packed in polystyrene boxes. The boxes were subjected to a temperature of-70 o C. After freezing for a period of time ranging from one to 12 months, cultured epithelial samples were assessed for their viability by vital staining (Trypan blue) and metabolic analysis based on glucose consumption and lactate production. Samples of not frozen cultured epithelium (Group B) were also tested for viability and the results obtained were used as comparison parameter for the variation of viability. RESULTS:Statistical analysis between the group A and B indicate that the mean age of the donors (p=0.51) and the culture time (p=1.18) showed no statistical difference. In 30 days we obtained 37% of the original viability of cultured epithelium, 25% at six months and one year, less than 15%. This trend was confirmed statistically with a reduction of approximately 1.8% of the original viability epithelium cultured every 30 days of storage. In the analysis by lactate production, similar results were observed. In the analysis by the glucose consumption results were not significant. The viability indices show statistically significant difference between the group A and B (p<0.0001). CONCLUSIONS:Although cryopreserved cultured epithelium showed significant reduction of viability, all samples remained viable. It was also found that the viability of cryopreserved cultured epithelial decreased as a function of storage time.

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“…However, although early reports of successful keratinocyte allograft transplantation 4,7 were supported by the finding that recipient blood group antigen expression was absent on epidermal cells at the allografted site and by the lack of stimulation of the mixed epidermal cell lymphocyte reaction between donor keratinocytes and recipient lymphocytes, 8 more recent investigations have failed to provide convincing evidence that the surviving grafted keratinocytes are of donor origin even though frank allograft rejection is not observed. [9][10][11][12][13] It is now well established that allografts may be rejected even in the absence of direct allopresentation (lack of professional donor antigen-presenting cells) via the indirect allopresentation pathway mediated by host antigen-presenting cells that infiltrate the graft within 2 weeks following transplantation and pick up donor alloantigens (especially MHC class I molecules (MHCI)), and present them to host T cells in the draining lymph nodes. These controversial results have highlighted the difficulties in establishing whether keratinocyte allografts can be used for more than a temporary skin covering.…”

Section: Introductionmentioning

confidence: 99%

Intrabody-mediated phenotypic knockout of major histocompatibility complex class I expression in human and monkey cell lines and in primary human keratinocytes

et al. 2002

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Multicentre experience in the treatment of burns with autologous and allogenic cultured epithelium, fresh or preserved in a frozen state

Cited by 247 publications

References 11 publications

Long-Term Type VII Collagen Restoration to Human Epidermolysis Bullosa Skin Tissue

Long-Term Type VII Collagen Restoration to Human Epidermolysis Bullosa Skin Tissue

An outcome analysis and long-term viability of cryopreserved cultured epidermal allografts: assessment of the conservation of transplantable human skin allografts

Intrabody-mediated phenotypic knockout of major histocompatibility complex class I expression in human and monkey cell lines and in primary human keratinocytes

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