Biniazan Felor, Rajaei Farzad, Darabi Shahram, Babajani Amirhesam, Mashayekhi Mahboubeh, Vousooghi Nasim, Abdollahifar Mohammad-Amin, Salimi Maryam, Niknejad Hassan
Cellular and Molecular Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran.
Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Stem Cell Rev Rep. 2022 Aug;18(6):2045-2058. doi: 10.1007/s12015-022-10355-7. Epub 2022 Mar 18.
Pressure ulcers (PUs), a result of ischemic reperfusion (IR) injuries, are prevalent skin problems which show refractoriness against standard therapeutic approaches. Besides, scar formation is a critical complication of ulcers that affects functionality and the skin's cosmetic aspect. The current study aimed to investigate the effects of placenta-derived human amniotic epithelial cells (hAECs), as important agents of regenerative medicine and stem cell therapy, on accelerating the healing of IR ulcers in mice. We also evaluated the effects of these cells on reducing the TGFβ-induced scar formation.
Male Balb/c mice at the age of 6-8 weeks were subjected to three IR cycles. Afterward, the mice were divided into three experimental groups (n = 6 per group), including the control group, vehicle group, and hAECs treatment group. Mice of the treatment group received 100 μL of fresh hAECs 1 × 10 cell/ml suspension in PBS. Afterward, mice were assessed by histological, stereological, molecular, and western blotting techniques at 3, 7, 14, and 21 days after wounding.
The histological and stereological results showed the most diminutive scar formation and better healing in the hAECs treated group compared to control group. Furthermore, our results demonstrated that the expression level of Col1A1 on days 3, 14, and 21 in the hAECs treated group was significantly lower than control. Additionally, injection of hAECs significantly reduced the expression level of Col3A1 on days 3, 7, and 21 while increased Col3A1 on the day 14. Otherwise, in the hAECs treated group, the expression levels of VEGFA on days 7 and 14 were higher, which showed that hAECs could promote angiogenesis and wound healing. Also, cell therapy significantly lowered the protein levels of TGF-β1 on day 14, while the protein level of TGF-β3 on day 14 was significantly higher. This data could demonstrate the role of hAECs in scar reduction in IR wounds.
These results suggest that hAECs can promote re-epithelialization and wound closure in an animal model of PU. They also reduced scar formation during wound healing by reducing the expression of TGF-β1/ TGF-β3 ratio.
压疮（PUs）是缺血再灌注（IR）损伤的结果，是常见的皮肤问题，对标准治疗方法具有难治性。此外，瘢痕形成是溃疡的关键并发症，会影响功能和皮肤外观。本研究旨在探讨胎盘来源的人羊膜上皮细胞（hAECs）作为再生医学和干细胞治疗的重要因子，对加速小鼠IR溃疡愈合的影响。我们还评估了这些细胞对减少转化生长因子β（TGFβ）诱导的瘢痕形成的作用。
将6 - 8周龄的雄性Balb/c小鼠进行三个IR周期处理。之后，将小鼠分为三个实验组（每组n = 6），包括对照组、载体组和hAECs治疗组。治疗组小鼠接受100 μL PBS中1×10⁶细胞/ml的新鲜hAECs悬浮液。之后，在受伤后3、7、14和21天通过组织学、体视学、分子和蛋白质印迹技术对小鼠进行评估。
组织学和体视学结果显示，与对照组相比，hAECs治疗组瘢痕形成最小，愈合更好。此外，我们的结果表明，hAECs治疗组在第3、14和21天的Col1A1表达水平显著低于对照组。此外，注射hAECs在第3、7和21天显著降低了Col3A1的表达水平，而在第14天增加了Col3A1的表达。否则，在hAECs治疗组中，第7和14天的VEGFA表达水平较高，这表明hAECs可以促进血管生成和伤口愈合。此外，细胞治疗在第14天显著降低了TGF-β1的蛋白水平，而第14天TGF-β3的蛋白水平显著升高。这些数据可以证明hAECs在减少IR伤口瘢痕中的作用。
这些结果表明，hAECs可以促进PU动物模型中的上皮再形成和伤口闭合。它们还通过降低TGF-β1/TGF-β3比值的表达减少伤口愈合过程中的瘢痕形成。
