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在小鼠中,异体成纤维细胞片促进皮肤伤口愈合的效果与自体成纤维细胞片相当。

Allogeneic fibroblast sheets accelerate cutaneous wound healing equivalent to autologous fibroblast sheets in mice.

作者信息

Nagase Takashi, Ueno Koji, Mizoguchi Takahiro, Samura Makoto, Harada Takasuke, Suehiro Kotaro, Shirasawa Bungo, Morikage Noriyasu, Hamano Kimikazu

机构信息

Department of Surgery and Clinical Sciences, Graduate School of Medicine, Yamaguchi University Ube, Yamaguchi, Japan.

Department of Medical Education, Yamaguchi University Graduate School of Medicine Ube, Japan.

出版信息

Am J Transl Res. 2020 Jun 15;12(6):2652-2663. eCollection 2020.

PMID:32655797
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7344096/
Abstract

BACKGROUND/AIMS: This study sought to confirm the difference of the wound-healing effect, cell survival, and immune response between autologous fibroblast sheets and allogeneic fibroblast sheets.

METHODS

Regarding wound healing, autologous or allogeneic fibroblast sheets were transplanted onto a mouse cutaneous wound healing model and the wound contraction rate was evaluated. The luciferase-expressing fibroblast sheet was prepared and the survival of the cell sheet was evaluated by IVIS after autologous or allogeneic transplantation. Histological evaluation was performed at five and 14 days after transplantation.

RESULTS

Allogeneic fibroblast-sheet transplantation showed significant wound contraction at the early phase of wound healing, which was equivalent to that seen with the autologous fibroblast sheets. Luminescence of the autologous and allogeneic luciferase-expressing fibroblast sheets peaked on Day 5, and no luminescence was observed on Day 13. In the allogeneic fibroblast-sheet transplant group, a significant accumulation of immune cells was observed in the healed tissue but not in the early stage of wound healing.

CONCLUSION

The allogeneic fibroblast sheets showed comparable rates of cell survival and wound-healing effects to those of the autologous fibroblast sheets, despite the subsequent immunogenic response. This result supports the potential practical clinical application of scaffold-free allogeneic fibroblast sheets based on the paracrine effect.

摘要

背景/目的:本研究旨在确认自体成纤维细胞片和异体成纤维细胞片在伤口愈合效果、细胞存活及免疫反应方面的差异。

方法

关于伤口愈合,将自体或异体成纤维细胞片移植到小鼠皮肤伤口愈合模型上,并评估伤口收缩率。制备表达荧光素酶的成纤维细胞片,在自体或异体移植后通过IVIS评估细胞片的存活情况。在移植后第5天和第14天进行组织学评估。

结果

异体成纤维细胞片移植在伤口愈合早期显示出显著的伤口收缩,这与自体成纤维细胞片所见相当。自体和异体表达荧光素酶的成纤维细胞片的发光在第5天达到峰值,在第13天未观察到发光。在异体成纤维细胞片移植组中,在愈合组织中观察到免疫细胞显著聚集,但在伤口愈合早期未观察到。

结论

尽管随后会发生免疫原性反应,但异体成纤维细胞片显示出与自体成纤维细胞片相当的细胞存活率和伤口愈合效果。这一结果支持了基于旁分泌效应的无支架异体成纤维细胞片在临床实际应用中的潜力。

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本文引用的文献

1
Fibroblasts as a practical alternative to mesenchymal stem cells.成纤维细胞作为间充质干细胞的实用替代品。
J Transl Med. 2018 Jul 27;16(1):212. doi: 10.1186/s12967-018-1536-1.
2
Treatment of Cutaneous Ulcers with Multilayered Mixed Sheets of Autologous Fibroblasts and Peripheral Blood Mononuclear Cells.用自体成纤维细胞和外周血单个核细胞多层混合片治疗皮肤溃疡
Cell Physiol Biochem. 2018;47(1):201-211. doi: 10.1159/000489767. Epub 2018 May 10.
3
Ulcer healing effect of autologous mixed sheets consisting of fibroblasts and peripheral blood mononuclear cells in rabbit ischemic hind limb.由成纤维细胞和外周血单个核细胞组成的自体混合片对兔缺血后肢的溃疡愈合作用
Am J Transl Res. 2017 May 15;9(5):2340-2351. eCollection 2017.
4
Prevalence and incidence of chronic wounds and related complications: a protocol for a systematic review.慢性伤口及其相关并发症的患病率和发病率:一项系统评价方案
Syst Rev. 2016 Sep 8;5(1):152. doi: 10.1186/s13643-016-0329-y.
5
Treatment of refractory cutaneous ulcers with mixed sheets consisting of peripheral blood mononuclear cells and fibroblasts.用外周血单个核细胞和成纤维细胞混合片治疗难治性皮肤溃疡。
Sci Rep. 2016 Jun 22;6:28538. doi: 10.1038/srep28538.
6
Challenges in the Treatment of Chronic Wounds.慢性伤口治疗中的挑战。
Adv Wound Care (New Rochelle). 2015 Sep 1;4(9):560-582. doi: 10.1089/wound.2015.0635.
7
Management of mixed arterial venous lower extremity ulceration: A review.下肢动静脉混合性溃疡的管理:综述
Vasc Med. 2015 Oct;20(5):479-86. doi: 10.1177/1358863X15594683. Epub 2015 Jul 23.
8
Clinical challenges of chronic wounds: searching for an optimal animal model to recapitulate their complexity.慢性伤口的临床挑战:寻找一种能概括其复杂性的最佳动物模型。
Dis Model Mech. 2014 Nov;7(11):1205-13. doi: 10.1242/dmm.016782.
9
Fibroblasts in fibrosis: novel roles and mediators.纤维化中的成纤维细胞:新作用与介质
Front Pharmacol. 2014 May 27;5:123. doi: 10.3389/fphar.2014.00123. eCollection 2014.
10
Cell sheet approach for tissue engineering and regenerative medicine.细胞片层方法在组织工程和再生医学中的应用。
J Control Release. 2014 Sep 28;190:228-39. doi: 10.1016/j.jconrel.2014.05.024. Epub 2014 May 21.