27946 Comparison of Treatments with Local Mesenchymal Stem Cells and Mesenchymal Stem Cells with Increased Vascular Endothelial Growth Factor Expression On Irradiation Injury of Expanded Skin

Saturday, October 17, 2015: 8:50 AM
Sinan Öksüz, MD , Plastic and Reconstructive Surgery, Gulhane Military Medical Academy Haydarpasa Training Hospital, Istanbul, Turkey
Murat Sahin Alagoz, MD, PhD, Associate Professor , Plastic and Reconstructive Surgery, Kocaeli University School of Medicine, Kocaeli, Turkey
Huseyin Karagoz, MD, PhD , Plastic and Reconstructive Surgery, Gulhane Military Medical Academy, Haydarpasa Training Hospital, Istanbul, Turkey
Zafer Kucukodaci, MD, Associate Professor , Pathology, Gulhane Military Medical Academy Haydarpasa Training Hospital, Istanbul, Turkey
Erdal Karaoz, PhD, Professor , Institute of Health Sciences Center for Stem Cell and Gene Therapies, Kocaeli University, Kocaeli, Turkey
Gokhan Duruksu, PhD, Assistant Professor , Institute of Health Sciences Center for Stem Cell and Gene Therapies, Kocaeli University, Kocaeli, Turkey
Gorkem Aksu, MD, Associate Professor , Radiation Oncology, Kocaeli University, Kocaeli, Turkey
Muammer Urhan, MD, Associate Professor , Nuclear Medicine, Gulhane Military Medical Academy Haydarpasa Training Hospital, Istanbul, Turkey

BACKGROUND

Radiation injury results in chronically ischemic tissue. Radionecrosis can be encountered in severe cases. Mesenchymal stem cells (MSCs) have a therapeutic effect on ischemia-related lesions. In here, effects of bone-marrow derived MSC and vascular endothelial growth factor (VEGF) gene-transfected MSC (VEGF-MSC) treatment on expanded skin with irradiation injury is investigated.

METHODS

Silicone tissue expander (50cc) was placed subcutaneously and expanded weekly up to 60cc in 24 Sprague Dawley rats. Single fraction (30Gy) radiotherapy was applied to the 2x2cm area of the expanded skin. Dulbecco’s Modified Eagle Medium (DMEM) without cell component, MSCs, and VEGF-MSCs were injected subcutaneously at the irradiation-expansion sites. Skin samples were evaluated by histomorphometry and immunohistochemistry. Perfusion rate of the samples were assessed by scintigraphy.

RESULTS

Epidermal thickness of irradiated-expanded skin was increased after MSC and VEGF-MSC treatment whereas dermal and capsule thicknesses did not change. MSC and VEGF-MSC treatments were effective in preserving respectively CD31 and VEGF expressions at a similar level as expanded skin after irradiation injury. VEGF-MSC treatment significantly elevated CD31 levels in the irradiated tissue. Skin perfusion results were consistent with the CD31 and VEGF expressions. MSC and VEGF-MSC treatments were effective in increasing PCNA expression in irradiation zone. VEGF-MSC treatment was efficient in reducing both expansion- and irradiation-related apoptosis.

CONCLUSION

Vascular impairment and dermal insufficiency due to tissue expansion and irradiation injury can easily result in a wound hard to repair. MSCs and VEGF-MSCs can promote neo-vascularization, reverse the effect of irradiation, and provide more durable soft tissue for expansion/implant reconstruction.