About ATMPs, SOPs and GMP: The Hurdles to Produce Novel Skin Grafts for Clinical Use

Hartmann-Fritsch, Fabienne; Marino, Daniela; Ernst, Rolf

doi:10.1159/000447645

Cited by 27 publications

(26 citation statements)

References 25 publications

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“…Skin defects are often caused by acute and chronic disease ( 1 ). It is difficult to achieve satisfactory treatment for patients with skin defects that encompass a large area ( 2 ). With the development of skin tissue engineering, a novel method for wound healing can be provided ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

miR‑339‑5p negatively regulates loureirin A‑induced hair follicle stem cell differentiation by targeting DLX5

Xie

et al. 2018

Mol Med Report

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Our previous study indicated that loureirin A induces hair follicle stem cell (HFSC) differentiation through Wnt/β-catenin signaling pathway activation. However, if and how microRNAs (miRNAs/miRs) modulate loureirin A-induced differentiation remains to be elucidated. In the present study, HFSCs were separated from the vibrissae of rats and identified by CD34 and keratin, type 1 cytoskeletal (K)15 expression. Microarray-based miRNA profiling analysis revealed that miR-339-5p was downregulated in loureirin A-induced HFSC differentiation. miR-339-5p overexpression by transfection with miR-339-5p mimics markedly inhibited the expression of K10 and involucrin, which are markers of epidermal differentiation, whereas inhibition of miR-339-5p by miR-339-5p inhibitor transfection promoted the expression of K10 and involucrin. These results suggest that miR-339-5p is a negative regulator of HFSC differentiation following induction by loureirin A. These findings were confirmed by a luciferase assay. Homeobox protein DLX-5 (DLX5) was identified as a direct target of miR-339-5p. Furthermore, it was demonstrated that miR-339-5p inhibited DLX5. Overexpression of miR-339-5p by mimic transfection significantly inhibited protein Wnt-3a (Wnt3a) expression, while inhibition of miR-339-5p by inhibitor transfection significantly increased the expression of Wnt3a. Furthermore, small interfering RNA targeting DLX5 was transfected into HFSCs, and western blot analysis revealed that Wnt3a, involucrin and K10 expression was significantly downregulated. Taken together, these results suggest that miR-339-5p negatively regulated loureirin A-induced HFSC differentiation by targeting DLX5, resulting in Wnt/β-catenin signaling pathway inhibition. This may provide a possible therapeutic target for skin repair and regeneration.

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Section: Introductionmentioning

confidence: 99%

miR‑339‑5p negatively regulates loureirin A‑induced hair follicle stem cell differentiation by targeting DLX5

Xie

et al. 2018

Mol Med Report

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“…(iii) After approximately two weeks, the culture conditions are switched from submerged to air liquid interface (ALI) in order to promote the stratification of the epidermis with the formation of the stratum corneum [2,69]. Such full-thickness engineered skin can be eventually implanted, but different requirements need to be satisfied [70]. The engineered skin must be safe for the patient because any cultured cell material possesses an associated risk of contamination, and viral or bacterial infection.…”

Section: Traditional Tissue Engineeringmentioning

confidence: 99%

“…One of the strengths of the tissue engineering approach is the possibility to have fine control over the properties of the final tissue. Indeed, by modulating the initial properties of the scaffold used to accommodate human fibroblasts and optimizing the culture conditions (culture media composition, mechanical stimulation, hydrodynamic stimulation) it is possible to obtain engineered skin with desired properties [10,38,[47][48][49]70]. It has been demonstrated that uniaxial and biaxial stretch can induce the alignment of the de novo synthesized collagen network [73].…”

Section: Traditional Tissue Engineeringmentioning

confidence: 99%

Bioengineered Skin Substitutes: The Role of Extracellular Matrix and Vascularization in the Healing of Deep Wounds

Urciuolo

Casale

Imparato

et al. 2019

JCM

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The formation of severe scars still represents the result of the closure process of extended and deep skin wounds. To address this issue, different bioengineered skin substitutes have been developed but a general consensus regarding their effectiveness has not been achieved yet. It will be shown that bioengineered skin substitutes, although representing a valid alternative to autografting, induce skin cells in repairing the wound rather than guiding a regeneration process. Repaired skin differs from regenerated skin, showing high contracture, loss of sensitivity, impaired pigmentation and absence of cutaneous adnexa (i.e., hair follicles and sweat glands). This leads to significant mobility and aesthetic concerns, making the development of more effective bioengineered skin models a current need. The objective of this review is to determine the limitations of either commercially available or investigational bioengineered skin substitutes and how advanced skin tissue engineering strategies can be improved in order to completely restore skin functions after severe wounds.

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“…Human primary fibroblasts and keratinocytes were isolated as previously described. 11 Isolation and cell culture was performed in a clean room laboratory class A, in line with good manufacturing practice (GMP) guidelines, 32 according to the defined standard operating procedures and in compliance with the established quality management system. Cell cultures were performed from four independent donor samples.…”

Section: Cell Isolation and Culturementioning

confidence: 99%

The Effect of Wound Dressings on a Bio-Engineered Human Dermo-Epidermal Skin Substitute in a Rat Model

Hüging

Biedermann

Sobrio

et al. 2017

Journal of Burn Care & Research

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Autologous bio-engineered dermo-epidermal skin substitutes are a promising treatment for large skin defects such as burns. For their successful clinical application, the graft dressing must protect and support the keratinocyte layer and, in many cases, possess antimicrobial properties. However, silver in many antimicrobial dressings may inhibit keratinocyte growth and differentiation. The purpose of our study was to evaluate the effect of various wound dressings on the healing of a human hydrogel-based dermo-epidermal skin substitute in preparation for the first-in-human clinical trials. Human dermo-epidermal skin substitutes approved for clinical trials were produced under good manufacturing practice conditions, transplanted onto immuno-incompetent rats, and dressed with either Vaseline Gauze™ (Kendall Medtronic, Minneapolis, USA), Suprathel (PolyMedics Innovations GmbH, Denkendorf, Germany), Urgotul SSD (Urgo Medical, Shepshed, United Kingdom), Mepilex AG (Mölnlycke Health Care, Gothenburg, Sweden), or Acticoat™ (Smith&Nephew, Baar, Switzerland). Grafts were assessed clinically for take, epithelialization, and infection at 10 and 21 days post-transplantation, and histologically at 21 days. There were three subjects each in the Vaseline Gauze™ and Suprathel groups, and four subjects each in the Urgotul SSD, Mepilex AG, and Acticoat™ groups. For all samples, the take rate was 100% and the expected keratinocyte number, epithelialization and epidermal stratification were observed. All of the dressings in the current study were well tolerated by our human dermo-epidermal skin substitute. The tolerance of the silver-based dressings is particularly relevant given the high risk of bacterial contamination with large skin defects, and provides pivotal information as we embark on clinical trials for this novel skin substitute.

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About ATMPs, SOPs and GMP: The Hurdles to Produce Novel Skin Grafts for Clinical Use

Cited by 27 publications

References 25 publications

miR‑339‑5p negatively regulates loureirin A‑induced hair follicle stem cell differentiation by targeting DLX5

miR‑339‑5p negatively regulates loureirin A‑induced hair follicle stem cell differentiation by targeting DLX5

Bioengineered Skin Substitutes: The Role of Extracellular Matrix and Vascularization in the Healing of Deep Wounds

The Effect of Wound Dressings on a Bio-Engineered Human Dermo-Epidermal Skin Substitute in a Rat Model

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