克隆间充质基质细胞衍生的不同细胞外囊泡亚群对伤口愈合过程中培养成纤维细胞的影响比较。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology Pub Date : 2025-01-17 DOI:10.1016/j.biocel.2025.106737

Hedie Poorkazem , Maryam Saber , Azadeh Moradmand , Saeed Yakhkeshi , Homeyra Seydi , Ensiyeh Hajizadeh-Saffar , Faezeh Shekari , Seyedeh-Nafiseh Hassani

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引用次数: 0

摘要

未愈合的伤口构成重大挑战，需要有效的治疗干预。细胞外囊泡（EVs）是一种很有前途的无细胞治疗药物。然而，不同亚群ev在伤口愈合中的功能差异仍未得到充分研究。本研究旨在评估克隆间充质基质细胞（cMSC）衍生的两个不同亚群，即20K和110k -cMSC- ev，主要对体外伤口愈合过程的影响，为动物模型提供快速和经济的替代方案。方法：比较高速离心分离的20K和差动超离心分离的110k - cscs - ev的体外作用。评估伤口愈合的主要机制，包括细胞增殖、细胞迁移、血管生成和收缩。人真皮成纤维细胞（HDF）被认为是分析这些过程的主要细胞。此外，我们还进行了基因表达分析，以评估这些EV亚群对HDF伤口愈合相关过程的影响。结果：20K和110k的cmsc - ev对细胞增殖、细胞迁移、血管生成和凝胶收缩均有良好的促进作用。RT-qPCR结果显示，两种EV类型均下调白细胞介素6 (IL6)，通过上调增殖细胞核抗原（PCNA）诱导增殖，通过上调基质金属肽酶1 （MMP1）和下调1型胶原蛋白（COL1）调节细胞重塑。讨论：本研究强调了20K和110k - cmsc - ev对伤口愈合相关过程中HDFs效力的影响。值得注意的是，20k - cmsc - ev为分离提供了更可行和更具成本效益的亚群，并符合GMP标准，建议将该部分用于治疗应用。

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Comparative effects of various extracellular vesicle subpopulations derived from clonal mesenchymal stromal cells on cultured fibroblasts in wound healing-related process

Introduction

Non-healing wounds pose significant challenges and require effective therapeutic interventions. Extracellular vesicles (EVs) have emerged as promising cell-free therapeutic agents in tissue regeneration. However, the functional differences between different subpopulations of EVs in wound healing remain understudied. This study aimed to evaluate the effects of two distinct subpopulations of clonal mesenchymal stromal cells (cMSC)-derived EVs (cMSC-EVs), namely 20 K and 110K-cMSC-EVs, primarily on in vitro wound healing process, providing fast and cost-effective alternatives to animal models.

Methods

In vitro assays were conducted to compare the effects of 20 K and 110K-cMSC-EVs, isolated through high-speed centrifugation and differential ultracentrifugation, respectively. For evaluation the main mechanisms of wound healing, including cell proliferation, cell migration, angiogenesis, and contraction. Human dermal fibroblasts (HDF) were considered as the main cells for analysis of these procedures. Moreover, gene expression analysis was performed to assess the impact of these EV subpopulations on the related process of wound healing on HDF.

Results

The results demonstrated that both 20 K and 110K-cMSC-EVs exhibited beneficial effects on cell proliferation, cell migration, angiogenesis, and gel contraction. RT-qPCR revealed that both EV types downregulated interleukin 6 (IL6), induced proliferation by upregulating proliferating cell nuclear antigen (PCNA), and regulated remodeling by upregulating matrix metallopeptidase 1 (MMP1) and downregulating collagen type 1 (COL1).

Discussion

This study highlights the effects of both 20 K and 110K-cMSC-EVs on the potency of HDFs in wound healing-related process. As the notable finding, 20K-cMSC-EVs offer a more feasible and cost-effective subpopulation for isolation and follow the GMP standard, recommended to utilize this fraction for therapeutic application.

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来源期刊

International Journal of Biochemistry & Cell Biology 生物-生化与分子生物学

CiteScore

8.10

自引率

0.00%

发文量

124

审稿时长

19 days

期刊介绍： IJBCB publishes original research articles, invited reviews and in-focus articles in all areas of cell and molecular biology and biomedical research. Topics of interest include, but are not limited to: -Mechanistic studies of cells, cell organelles, sub-cellular molecular pathways and metabolism -Novel insights into disease pathogenesis -Nanotechnology with implication to biological and medical processes -Genomics and bioinformatics