Therapeutic Effects of Human Adipose-Derived Products on Impaired Wound Healing in Irradiated Tissue
Therapeutic Effects of Human Adipose-Derived Products on Impaired Wound Healing in Irradiated Tissue
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DOI：
10.1097/prs.0000000000004609
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发表时间：
2018-08-01
影响因子：
3.6
通讯作者：
Yoshimura, Kotaro
中科院分区：
文献类型：
--
作者：
Wu, Szu-Hsien;Shirado, Takako;Yoshimura, Kotaro
背景：辐射的临床后遗症导致组织失活（例如，局部缺血、纤维化和萎缩），其中伤口愈合能力受损。脂肪衍生的产品可能会工作，以治疗这样的pathology.Methods：非致死性照射在不同剂量（5，10，和15戈伊）和频率（一至三次连续几天）被传递到裸鼠背部皮肤，随后的肉眼和显微镜下的变化进行了评估，长达4周。然后创建皮肤打孔伤口，以比较辐照和非辐照状态下的伤口愈合。伤口也局部注射车辆，培养的脂肪来源的干细胞，离心脂肪组织，或微粉化细胞脂肪基质，和治疗的影响进行了监测长达15 days.Results：裸小鼠给予总剂量大于15戈伊自发地发展皮肤溃疡，辐射损伤是剂量依赖性的，但是，一个分次照射协议能够减少损害。组织学评估显示剂量依赖性真皮纤维化/增厚和皮下萎缩。伤口愈合的剂量依赖性（5至15戈伊）损害也很明显。在最高剂量（15戈伊，三次）下，开放性伤口在第15天持续存在。然而，注射培养的脂肪源性干细胞的伤口在第12天几乎愈合，并且注射离心脂肪或微粉化组织的伤口比未处理的对照愈合得更快（p < 0.05）。有治疗groups.Conclusions之间没有显着差异：组织灭活辐射是剂量依赖性的，虽然分馏协议有助于减少it. Adipose-derived干细胞和其他脂肪衍生产品窝藏脂肪衍生干细胞成功地振兴辐照组织和加速伤口愈合。
Background: Clinical sequelae of irradiation result in tissue devitalization (e.g., ischemia, fibrosis, and atrophy) where wound healing capacity is impaired. Fat-derived products may work to treat such pathology.Methods: Nonlethal irradiation at various doses (5, 10, and 15 Gy) and frequencies (one to three times on sequential days) was delivered to dorsal skin of nude mice, and subsequent gross and microscopic changes were evaluated for up to 4 weeks. Cutaneous punch wounds were then created to compare wound healing in irradiated and nonirradiated states. Wounds were also locally injected with vehicle, cultured adipose-derived stem cells, centrifuged fat tissue, or micronized cellular adipose matrix, and the therapeutic impact was monitored for up to 15 days.Results: Nude mice given total doses greater than 15 Gy spontaneously developed skin ulcers, and radiation damage was dose-dependent; however, a fractionated irradiation protocol was able to reduce the damage. Histologic assessment revealed dose-dependent dermal fibrosis/thickening and subcutaneous atrophy. Dose-dependent (5 to 15 Gy) impairment of wound healing was also evident. At the highest dosage (15 Gy three times), open wounds persisted on day 15. However, wounds injected with cultured adipose-derived stem cells were nearly healed on day 12, and those treated with injection of centrifuged fat or micronized tissue healed faster than untreated controls (p < 0.05). There was no significant differences between treated groups.Conclusions: Tissue devitalization by irradiation was dose-dependent, although fractionated protocols helped to reduce it. Adipose-derived stem cells and other fat-derived products harboring adipose-derived stem cells successfully revitalized irradiated tissues and accelerated wound healing.