Zhou Zixuan, Xun Jingnan, Wu Chenghao, Ji Chao, Ji Shizhao, Shu Futing, Wang Yuxiang, Chen Hao, Zheng Yongjun, Xiao Shichu
Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, People's Republic of China.
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, People's Republic of China.
Mater Today Bio. 2023 Jun 7;20:100686. doi: 10.1016/j.mtbio.2023.100686. eCollection 2023 Jun.
Umbilical cord-derived mesenchymal stem cells (UC-MSC) are promising candidates for wound healing. However, the low amplification efficiency of MSC in vitro and their low survival rates after transplantation have limited their medical application. In this study, we fabricated a micronized amniotic membrane (mAM) as a microcarrier to amplify MSC in vitro and used mAM and MSC (mAM-MSC) complexes to repair burn wounds. Results showed that MSC could live and proliferate on mAM in a 3D culture system, exhibiting higher cell activity than in 2D culture. Transcriptome sequencing of MSC showed that the expression of growth factor-related, angiogenesis-related, and wound healing-related genes was significantly upregulated in mAM-MSC compared to traditional 2D-cultured MSC, which was verified via RT-qPCR. Gene ontology (GO) analysis of differentially expressed genes (DEGs) showed significant enrichment of terms related to cell proliferation, angiogenesis, cytokine activity, and wound healing in mAM-MSC. In a burn wound model of C57BL/6J mice, topical application of mAM-MSC significantly accelerated wound healing compared to MSC injection alone and was accompanied by longer survival of MSC and greater neovascularization in the wound.
脐带间充质干细胞(UC-MSC)是伤口愈合的有前景的候选者。然而,间充质干细胞在体外的扩增效率低以及移植后的低存活率限制了它们的医学应用。在本研究中,我们制备了一种微粉化羊膜(mAM)作为微载体以在体外扩增间充质干细胞,并使用mAM与间充质干细胞(mAM-MSC)复合物修复烧伤创面。结果显示,在三维培养系统中间充质干细胞能够在mAM上存活并增殖,表现出比二维培养更高的细胞活性。间充质干细胞的转录组测序表明,与传统二维培养的间充质干细胞相比,mAM-MSC中与生长因子相关、血管生成相关和伤口愈合相关的基因表达显著上调,这通过逆转录定量聚合酶链反应(RT-qPCR)得到验证。对差异表达基因(DEG)的基因本体(GO)分析表明,mAM-MSC中与细胞增殖、血管生成、细胞因子活性和伤口愈合相关的术语显著富集。在C57BL/6J小鼠的烧伤创面模型中,与单独注射间充质干细胞相比,局部应用mAM-MSC显著加速了伤口愈合,同时伴随着间充质干细胞更长时间的存活以及伤口中更多的新血管形成。