Use of gene-modified keratinocytes and fibroblasts to enhance regeneration in a full skin defect

Lohmeyer, Jörn Andreas; Liu, Fang; Krüger, Stefan; Lindenmaier, Werner; Siemers, Frank; Machens, Hans‐Günther

doi:10.1007/s00423-011-0761-3

Cited by 18 publications

(14 citation statements)

References 34 publications

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“…A few studies have been performed using VEGF to enhance wound healing. Altering fibroblast VEGF expression has shown potential increases in wound healing and angiogenesis[102,103]. Yet increasing VEGF has also been shown to increase fibrosis and scar formation in skin[104,105].…”

Section: Components Of a Skin Substitutementioning

confidence: 99%

Methodologies in creating skin substitutes

Nicholas

Jeschke

Amini-Nik

2016

Cell. Mol. Life Sci.

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The creation of skin substitutes has significantly decreased morbidity and mortality of skin wounds. Although there are still a number of disadvantages of currently available skin substitutes, there has been a significant decline in research advances over the past several years in improving these skin substitutes. Clinically most skin substitutes used are acellular and do not use growth factors to assist wound healing, key areas of potential in this field of research. This article discusses the five necessary attributes of an ideal skin substitute. It comprehensively discusses the three major basic components of currently available skin substitutes: scaffold materials, growth factors, and cells, comparing and contrasting what has been used so far. It then examines a variety of techniques in how to incorporate these basic components together to act as a guide for further research in the field to create cellular skin substitutes with clinically better results.

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Section: Components Of a Skin Substitutementioning

confidence: 99%

Methodologies in creating skin substitutes

Nicholas

Jeschke

Amini-Nik

2016

Cell. Mol. Life Sci.

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“…VEGF is a well-established therapeutic protein for enhancing angiogenesis both in vitro and in vivo . Our and many other groups have previously shown that secreted VEGF can enhance cell proliferation, wound healing and angiogenesis in different pre-clinical models [24, 49, 50]. In present study, our main focus was not on the effect of VEGF on proliferation of cells on scaffolds but rather if scaffolds can be used as carriers for cells which are genetically engineered to secrete VEGF or other therapeutic proteins.…”

Section: Discussionmentioning

confidence: 96%

Biodegradable poly (lactic acid-co-glycolic acid) scaffolds as carriers for genetically-modified fibroblasts

et al. 2017

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Recent advances in gene delivery into cells allow improved therapeutic effects in gene therapy trials. To increase the bioavailability of applied cells, it is of great interest that transfected cells remain at the application site and systemic spread is minimized. In this study, we tested clinically used biodegradable poly(lactic acid-co-glycolic acid) (PLGA) scaffolds (Vicryl & Ethisorb) as transient carriers for genetically modified cells. To this aim, we used human fibroblasts and examined attachment and proliferation of untransfected cells on the scaffolds in vitro, as well as the mechanical properties of the scaffolds at four time points (1, 3, 6 and 9 days) of cultivation. Furthermore, the adherence of cells transfected with green fluorescent protein (GFP) and vascular endothelial growth factor (VEGF165) and also VEGF165 protein secretion were investigated. Our results show that human fibroblasts adhere on both types of PLGA scaffolds. However, proliferation and transgene expression capacity were higher on Ethisorb scaffolds most probably due to a different architecture of the scaffold. Additionally, cultivation of the cells on the scaffolds did not alter their biomechanical properties. The results of this investigation could be potentially exploited in therapeutic regiments with areal delivery of transiently transfected cells and may open the way for a variety of applications of cell-based gene therapy, tissue engineering and regenerative medicine.

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“…These engineered skin components allowed for optimal conditions (otherwise both keratinocytes and fibroblasts lack support from other supporting cells) that led to a well-organized epidermis, structured dermis, and effective vascularization [18]. Of note, constant expression of the transgenes was apparently unnecessary, as transient levels mediated by the adenoviral vector were sufficient to enhance skin regeneration [18]. Finally, corneal allografts-as a direct consequence of their prolonged viability (up to four weeks without significant loss of function) prior to transplant-have been subjected to ex vivo gene therapy to prevent allograft rejection [19].…”

Section: Gene Modified Cellsmentioning

confidence: 98%

“…In one such study, both epidermal keratinocytes and dermal fibroblasts genetically modified to express important factors necessary for optimal skin repair: platelet-derived growth factor BB (PDGF-BB), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF). These engineered skin components allowed for optimal conditions (otherwise both keratinocytes and fibroblasts lack support from other supporting cells) that led to a well-organized epidermis, structured dermis, and effective vascularization [18]. Of note, constant expression of the transgenes was apparently unnecessary, as transient levels mediated by the adenoviral vector were sufficient to enhance skin regeneration [18].…”

Section: Gene Modified Cellsmentioning

confidence: 99%