Intralesional injection of adipose-derived stem cells reduces hypertrophic scarring in a rabbit ear model.
Intralesional injection of adipose-derived stem cells reduces hypertrophic scarring in a rabbit ear model.
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DOI：
10.1186/s13287-015-0133-y
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发表时间：
2015-08-18
影响因子：
7.5
通讯作者：
Cao WG
中科院分区：
文献类型：
--
作者：
Zhang Q;Liu LN;Yong Q;Deng JC;Cao WG
在愈合的皮肤伤口部位多余的胶原蛋白沉积导致增生性瘢痕。脂肪源性干细胞（ADSC）通过减少胶原沉积在各种抗纤维化应用中表现出希望。本研究旨在通过建立兔耳增生性瘢痕模型，探讨脂肪干细胞局部注射对瘢痕形成的影响。将12只新西兰白化病兔等分为3组，在每只耳上制造6个相同的穿孔缺损。在术后第14天，当所有伤口完全再上皮化时，第一组在其右耳上接受ADSC的病灶内注射，并在其左耳上接受Dulbecco改良的Eagle培养基（DMEM）作为内部对照。第二组兔右耳注射ADSCs-CM，左耳注射DMEM作为内对照。第三组的右耳保持未处理，左耳接受DMEM。我们在术后第14、21、28和35天用超声测量瘢痕升高指数（SEI）来量化瘢痕肥大。35天后收获伤口用于组织形态计量学和基因表达分析。与其内部对照相比，病灶内注射ADSC或ADSCs-CM均导致兔耳中具有更正常外观的瘢痕，并且显著降低SEI（分别为44.04%和32.48%，均P <0.01）。此外，根据组织形态计量学和实时定量聚合酶链反应分析，我们证实了胶原蛋白的组织更有规律，并且在ADSC和ADSCs-CM注射的瘢痕中α-平滑肌肌动蛋白（α-SMA）和I型胶原蛋白的表达减少。注射DMEM和未处理的瘢痕之间没有差异。病灶内注射ADSC通过降低α-SMA和I型胶原基因表达并改善胶原沉积来减少兔耳增生性瘢痕的形成，这可能导致有效且创新的抗瘢痕形成疗法。
Redundant collagen deposition at sites of healing dermal wounds results in hypertrophic scars. Adipose-derived stem cells (ADSCs) exhibit promise in a variety of anti-fibrosis applications by attenuating collagen deposition. The objective of this study was to explore the influence of an intralesional injection of ADSCs on hypertrophic scar formation by using an established rabbit ear model. Twelve New Zealand albino rabbits were equally divided into three groups, and six identical punch defects were made on each ear. On postoperative day 14 when all wounds were completely re-epithelialized, the first group received an intralesional injection of ADSCs on their right ears and Dulbecco’s modified Eagle’s medium (DMEM) on their left ears as an internal control. Rabbits in the second group were injected with conditioned medium of the ADSCs (ADSCs-CM) on their right ears and DMEM on their left ears as an internal control. Right ears of the third group remained untreated, and left ears received DMEM. We quantified scar hypertrophy by measuring the scar elevation index (SEI) on postoperative days 14, 21, 28, and 35 with ultrasonography. Wounds were harvested 35 days later for histomorphometric and gene expression analysis. Intralesional injections of ADSCs or ADSCs-CM both led to scars with a far more normal appearance and significantly decreased SEI (44.04 % and 32.48 %, respectively, both P <0.01) in the rabbit ears compared with their internal controls. Furthermore, we confirmed that collagen was organized more regularly and that there was a decreased expression of alpha-smooth muscle actin (α-SMA) and collagen type Ι in the ADSC- and ADSCs-CM-injected scars according to histomorphometric and real-time quantitative polymerase chain reaction analysis. There was no difference between DMEM-injected and untreated scars. An intralesional injection of ADSCs reduces the formation of rabbit ear hypertrophic scars by decreasing the α-SMA and collagen type Ι gene expression and ameliorating collagen deposition and this may result in an effective and innovative anti-scarring therapy.