新型双层细胞贴剂，结合表皮干细胞和血管生成脂肪干细胞，用于糖尿病创面愈合。

Novel bilayer cell patch combining epidermal stem cells and angiogenic adipose stem cells for diabetic wound healing.

机构信息

Department of Vascular Surgery, General Surgery Clinical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Cardiology, Third Affiliated Hospital of Soochow University, Changzhou, China.

出版信息

J Control Release. 2023 Jul;359:315-325. doi: 10.1016/j.jconrel.2023.06.010. Epub 2023 Jun 14.

DOI:10.1016/j.jconrel.2023.06.010

PMID:37315690

Abstract

Diabetic foot ulcer (DFU) is one of the most severe complications in patients with diabetes. However, the development of a promising therapeutic strategy for DFU is still challenging. In this article, we demonstrate a novel bilayer cell patch, and its therapeutic effects on diabetic wound healing have been systematically investigated. The experimental results revealed that diabetes mellitus exosomes (DM-Exos) could inhibit wound healing in normal C57/B6 mice. We identified three microRNAs (miRs) including miR-15a, miR-16, and miR-214 as anti-angiogenesis factors in DM-Exos. Furthermore, angiogenic-modified adipose stem cells (ADSCs, transfected with antagomiR-15a, antagomiR-16, and antagomiR-214) were found to enhance the angiogenesis ability of human umbilical vein endothelial cells (HUVECs) by co-culture. In addition, our findings exhibited that the bilayer cell patch combining epidermal stem cells (EpSCs) and angiogenic-modified ADSCs transplantation could promote diabetic wound healing through enhancing angiogenesis and re-epithelization. These findings illustrate that the novel bilayer cell patch has great potential in diabetic wound healing.

摘要

糖尿病足溃疡（DFU）是糖尿病患者最严重的并发症之一。然而，开发有前景的 DFU 治疗策略仍然具有挑战性。在本文中，我们展示了一种新型双层细胞贴片，并系统研究了其在糖尿病伤口愈合中的治疗效果。实验结果表明，糖尿病细胞外囊泡（DM-Exos）可抑制正常 C57/B6 小鼠的伤口愈合。我们鉴定出 DM-Exos 中的三种 microRNAs（miRs），包括 miR-15a、miR-16 和 miR-214，作为抗血管生成因子。此外，通过共培养发现转染 antagomiR-15a、antagomiR-16 和 antagomiR-214 的血管生成修饰脂肪干细胞（ADSCs）可增强人脐静脉内皮细胞（HUVECs）的血管生成能力。此外，我们的研究结果表明，结合表皮干细胞（EpSCs）和血管生成修饰 ADSCs 移植的新型双层细胞贴片可通过促进血管生成和再上皮化来促进糖尿病伤口愈合。这些发现表明，新型双层细胞贴片在糖尿病伤口愈合中有很大的潜力。