增强基因组编辑间充质干细胞与血小板之间的相互作用可改善小鼠的伤口愈合。

IF 6.7 1区 工程技术 Q1 CELL & TISSUE ENGINEERING Journal of Tissue Engineering Pub Date : 2024-09-23 eCollection Date: 2024-01-01 DOI:10.1177/20417314241268917
De-Yong Li, Yu-Meng Li, Dan-Yi Lv, Tian Deng, Xin Zeng, Lu You, Qiu-Yu Pang, Yi Li, Bing-Mei Zhu
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引用次数: 0

摘要

伤口愈合受损给医疗系统和患者带来了沉重负担。干细胞疗法在治疗伤口方面具有广阔的前景。然而,细胞归巢的低效率阻碍了它的临床应用。在这项研究中,我们利用基于Cas9-AAV6的基因组编辑工具平台,成功地将P-选择素糖蛋白配体-1(PSGL-1)整合到人脂肪间充质干细胞(ADSCs)的基因组中。我们的研究结果表明,PSGL-1基因敲入增强了ADSCs与血小板的结合及其对损伤部位的粘附。此外,静脉注射PSGL-1基因工程ADSCs(KI-ADSCs)可显著提高小鼠皮损部位的归巢效率和存活率。从机理上讲,PSGL-1敲入可通过激活典型的WNT/β-catenin信号通路来促进一些治疗性细胞因子的释放,并通过促进伤口部位的血管生成、再上皮化和肉芽组织形成来加速伤口愈合。这项研究为同时解决间充质干细胞迁移和粘附能力差的问题提供了一种新策略。
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Enhanced interaction between genome-edited mesenchymal stem cells and platelets improves wound healing in mice.

Impaired wound healing poses a significant burden on the healthcare system and patients. Stem cell therapy has demonstrated promising potential in the treatment of wounds. However, its clinical application is hindered by the low efficiency of cell homing. In this study, we successfully integrated P-selectin glycoprotein ligand-1 (PSGL-1) into the genome of human adipose-derived mesenchymal stem cells (ADSCs) using a Cas9-AAV6-based genome editing tool platform. Our findings revealed that PSGL-1 knock-in enhanced the binding of ADSCs to platelets and their adhesion to the injured site. Moreover, the intravenous infusion of PSGL-1 -engineered ADSCs (KI-ADSCs) significantly improved the homing efficiency and residence rate at the site of skin lesions in mice. Mechanistically, PSGL-1 knock-in promotes the release of some therapeutic cytokines by activating the canonical WNT/β-catenin signaling pathway and accelerates the healing of wounds by promoting angiogenesis, re-epithelialization, and granulation tissue formation at the wound site. This study provides a novel strategy to simultaneously address the problem of poor migration and adhesion of mesenchymal stem cells (MSCs).

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来源期刊
Journal of Tissue Engineering
Journal of Tissue Engineering Engineering-Biomedical Engineering
CiteScore
11.60
自引率
4.90%
发文量
52
审稿时长
12 weeks
期刊介绍: The Journal of Tissue Engineering (JTE) is a peer-reviewed, open-access journal dedicated to scientific research in the field of tissue engineering and its clinical applications. Our journal encompasses a wide range of interests, from the fundamental aspects of stem cells and progenitor cells, including their expansion to viable numbers, to an in-depth understanding of their differentiation processes. Join us in exploring the latest advancements in tissue engineering and its clinical translation.
期刊最新文献
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