局部间充质干细胞与血管内皮生长因子表达增加的间充质干细胞对扩张皮肤辐射损伤治疗效果的比较

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.

作者信息

Öksüz Sinan, Alagöz Murat Şahin, Karagöz Hüseyin, Küçükodac Zafer, Karaöz Erdal, Duruksu Gökhan, Aksu Görkem

机构信息

From the *Department of Plastic, Reconstructive Surgery and Burn Unit, Haydarpasa Training Hospital, Gulhane Military Medical Academy, Istanbul; †Department of Plastic and Reconstructive Surgery, Kocaeli University Medical Faculty, Kocaeli; ‡Department of Pathology, Haydarpasa Training Hospital, Gulhane Military Medical Academy, Istanbul; §Kocaeli University Institute of Health Sciences Center for Stem Cell and Gene Therapies; and ∥Department of Radiation Oncology, Kocaeli University Medical Faculty, Kocaeli, Turkey.

出版信息

Ann Plast Surg. 2015 Aug;75(2):219-30. doi: 10.1097/SAP.0000000000000574.

DOI:10.1097/SAP.0000000000000574

PMID:26165573

Abstract

INTRODUCTION

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 (50 cm) was placed subcutaneously and expanded weekly up to 60 cm in 24 Sprague Dawley rats. Single fraction (30 Gy) radiotherapy was applied to the 2 × 2 cm area of the expanded skin. Dulbecco modified Eagle medium 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 was assessed by scintigraphy.

RESULTS

Epidermal thickness of irradiated-expanded skin was increased after MSC and VEGF-MSC treatments, whereas dermal and capsule thicknesses did not change. The MSC and VEGF-MSC treatments were effective in preserving, respectively, CD31 and VEGF expressions at a similar level as expanded skin after irradiation injury. The VEGF-MSC treatment significantly elevated CD31 levels in the irradiated tissue. Skin perfusion results were consistent with the CD31 and VEGF expressions. The MSC and VEGF-MSC treatments were effective in increasing proliferating cell nuclear antigen (PCNA) expression in irradiation zone. The 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. The MSCs and VEGF-MSCs can promote neovascularization, reverse the effect of irradiation, and provide more durable soft tissue for expansion/implant reconstruction.

摘要

引言

辐射损伤会导致组织长期缺血。严重情况下会出现放射性坏死。间充质干细胞（MSCs）对缺血相关病变具有治疗作用。在此，研究了骨髓来源的间充质干细胞和血管内皮生长因子（VEGF）基因转染的间充质干细胞（VEGF-MSC）治疗对受辐射损伤的扩张皮肤的影响。

方法

在24只Sprague Dawley大鼠皮下植入硅胶组织扩张器（50 cm），每周扩张一次，直至扩张至60 cm。对2×2 cm面积的扩张皮肤进行单次分割（30 Gy）放疗。在照射-扩张部位皮下注射无细胞成分的杜氏改良 Eagle 培养基、间充质干细胞和 VEGF-间充质干细胞。通过组织形态计量学和免疫组织化学评估皮肤样本。通过闪烁显像评估样本的灌注率。

结果

间充质干细胞和VEGF-间充质干细胞治疗后，受辐射扩张皮肤的表皮厚度增加，而真皮和包膜厚度未改变。间充质干细胞和VEGF-间充质干细胞治疗分别有效地将CD31和VEGF表达维持在与辐射损伤后扩张皮肤相似的水平。VEGF-间充质干细胞治疗显著提高了受辐射组织中的CD31水平。皮肤灌注结果与CD31和VEGF表达一致。间充质干细胞和VEGF-间充质干细胞治疗有效地增加了照射区域增殖细胞核抗原（PCNA）的表达。VEGF-间充质干细胞治疗有效地减少了与扩张和辐射相关的细胞凋亡。