Premium
Cell suspension cultures of allogenic keratinocytes are efficient carriers for ex vivo gene transfer and accelerate the healing of full‐thickness skin wounds by overexpression of human epidermal growth factor
Author(s) -
Vranckx Jan Jeroen,
Hoeller Daniela,
Velander Patrik E. M.,
Theopold Christoph F. P.,
Petrie Nicola,
Takedo Akira,
Eriksson Elof,
Yao Feng
Publication year - 2007
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1524-475x.2007.00272.x
Subject(s) - ex vivo , suspension culture , wound healing , gene transfer , microbiology and biotechnology , human skin , in vivo , keratinocyte , epidermal growth factor , suspension (topology) , epidermis (zoology) , cell culture , growth factor , chemistry , biology , gene , immunology , anatomy , receptor , biochemistry , genetics , mathematics , homotopy , pure mathematics
The concept of using growth factor therapy to induce wound repair has been endorsed in studies that show reduced growth factors in wound fluid from chronic and aged wounds. In this study, we used cell suspensions of allogenic keratinocytes as gene‐delivery vehicles for human epidermal growth factor (hEGF) and analyzed their impact on wound repair in a porcine wound‐healing model. Full‐thickness wounds were created on the backs of six Yorkshire pigs and covered with a wound chamber to create a wet wound‐healing environment. First, 5 × 10 5 allogenic, autogenic, or mixed keratinocytes were transplanted into wounds and healing parameters were analyzed. Second, we measured long‐term reepithelialization and contraction rates from day 8 until day 35. In the third experiment, allogenic keratinocytes were transfected with an hEGF‐expressing plasmid pCEP‐hEGF and transplanted in full‐thickness wounds to improve repair. Wounds treated with autogenic, allogenic, or mixed keratinocytes showed a significantly higher rate of reepithelialization relative to saline‐treated control wounds. Repetitive biopsies indicated that the use of allogenic keratinocytes did not lead to long‐term wound breakdown. Wounds treated with hEGF‐expressing allogenic keratinocytes reepithelialized faster than wounds treated with allogenic keratinocytes or control wounds. With a peak hEGF expression of 920.8 pg/mL, hEGF was detectable until day 5 after transplantation compared with minimal hEGF expression in control wounds. This study shows that allogenic keratinocytes can serve as efficient gene transfer vehicles for ex vivo growth factor delivery to full‐thickness wounds and overexpression of hEGF further improves reepithelialization rates.