A review of gene and stem cell therapy in cutaneous wound healing

Abstract

Different therapies that effect wound repair have been proposed over the last few decades. This article reviews the emerging fields of gene and stem cell therapy in wound healing. Gene therapy, initially developed for treatment of congenital defects, is a new option for enhancing wound repair. In order to accelerate wound closure, genes encoding for growth factors or cytokines showed the greatest potential. The majority of gene delivery systems are based on viral transfection, naked DNA application, high pressure injection, or liposomal vectors. Embryonic and adult stem cells have a prolonged self-renewal capacity with the ability to differentiate into various tissue types. A variety of sources, such as bone marrow, peripheral blood, umbilical cord blood, adipose tissue, skin and hair follicles, have been utilized to isolate stem cells to accelerate the healing response of acute and chronic wounds. Recently, the combination of gene and stem cell therapy has emerged as a promising approach for treatment of chronic and acute wounds.

Figure 1

Levels of β-Galactosidase expression in porcine dermal and epidermal tissue as measure of gene transfection efficacy using multichannel confocal fluorescence imaging. (A–D) Control tissue. (E–H) Tissue transfected with Lac-Z cDNA delivered via liposomal vectors, Day 5 post-transfection. (A) Nuclei stained with 4′,6-diamidino-2-phenylindole (DAPI). (B) Fluorescein (FITC) β-Galactosidase expression. (C) Laser scanning brightfield image. (D) Overlay. (E) Nuclei stained with DAPI. (F) FITC β-Galactosidase Expression. (G) Laser scanning brightfield image. (H) Overlay – Composite image of DAPI, FITC, and brightfield to illustrate gross orientation of Lac-Z expression.

Figure 2

Photomicrographs of (A) Morphology of Cord Lining Epithelial Cells and (B) Cord Lining Mesenchymal Cells. Cells were isolated from the outer membrane of the umbilical cord and differentiated into both epithelial and mesenchymal cells using specific culture conditions. Magnification 200X.

Figure 3

Sections of rat skin samples (A) stained for β-galactosidase (blue) and (B) dual stained with anti-cyokeratin-19 antibodies using peroxidase immunohistochemical techniques (magnification 1000X). Alkaline Phosphatase was used as substrate, hence bright pink stained cells are CK-19 positive. Sections were lightly counterstained with hematoxylin (5 seconds) to identify nuclei. Section shows colocalization of CK-19 and Bluo-Gal stain in dermal sheath cells (marked DSC) along with hair follicle cells (ESC).