Autologous adipocyte derived stem cells favour healing in a minipig model of cutaneous radiation syndrome.

Autologous adipocyte derived stem cells favour healing in a minipig model of cutaneous radiation syndrome.
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自体脂肪细胞衍生的干细胞有利于皮肤辐射综合征的微型模型中的愈合。

DOI:
10.1371/journal.pone.0031694
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Drouet M
Drouet M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Forcheron F;Agay D;Scherthan H;Riccobono D;Herodin F;Meineke V;Drouet M

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皮肤辐射综合征(CRS)是局部皮肤暴露于高剂量电离辐射的延迟后果。在这里,我们首次在大型动物模型中研究了自体脂肪组织来源的基质细胞(ASCs)的治疗潜力。在实验中,Göttingen小型猪用50Gy60Co源进行局部伽玛射线照射,并移植(n = 5)或不移植(n = 8)。用含10%胎牛血清和碱性成纤维细胞生长因子(−-1)的MEM-α培养ASCs,照射后第25、46、67d皮内注射ASCs,第95~115d皮内注射ASCs(每次50×106ASCs)。所有对照组均表现出最终坏死的临床进展(第91天)。在移植猪中,观察到5只移植动物中有4只伤口最终愈合(第130+/−28天)。细胞角蛋白表达的免疫组织化学分析显示,表皮完全恢复。移植的ASCs聚集在真皮/皮下屏障,在那里它们吸引了大量的免疫细胞,甚至在一头猪身上增加了血管。总体而言,这项研究表明局部注射ASCs可能是缓解CRS的一种有用的策略。
Cutaneous radiation syndrome (CRS) is the delayed consequence of localized skin exposure to high doses of ionizing radiation. Here we examined for the first time in a large animal model the therapeutic potential of autologous adipose tissue-derived stroma cells (ASCs). For experiments, Göttingen minipigs were locally gamma irradiated using a 60Co source at the dose of 50 Gy and grafted (n = 5) or not (n = 8). ASCs were cultured in MEM-alpha with 10% fetal calf serum and basic fibroblast growth factor (2 ng.mL−1) and post irradiation were intradermally injected on days 25, 46, 67 and finally between days 95 and 115 (50×106 ASCs each time) into the exposed area. All controls exhibited a clinical evolution with final necrosis (day 91). In grafted pigs an ultimate wound healing was observed in four out of five grafted animals (day 130 +/− 28). Immunohistological analysis of cytokeratin expression showed a complete epidermis recovery. Grafted ASCs accumulated at the dermis/subcutis barrier in which they attracted numerous immune cells, and even an increased vasculature in one pig. Globally this study suggests that local injection of ASCs may represent a useful strategy to mitigate CRS.
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