We have collected the most exciting new researches in the field of genetics and cellular research in the past week.
Mesenchymal Stem Cell Derived Exosomes Therapy in Diabetic Wound Repair
Abstract
Nowadays, refractory diabetic wounds cause a worldwide medical burden. Mesenchymal stem cells derived exosomes (MSC-Exos) show promise as a solid alternative to existing therapeutics in the latest researches, since MSC-Exos share similar biologic activity but less immunogenicity when compared with MSCs. To facilitate further understanding and application, it is essential to summarize the current progress and limitations of MSC-Exos in the treatment of diabetic wounds. In this review, we introduce the effects of different MSC-Exos on diabetic wounds according to their origins and contents and discuss the specific experimental conditions, target wound cells/pathways, and specific mechanisms. In addition, this paper focuses on the combination of MSC-Exos and biomaterials, which improves the efficacy and utilization of MSC-Exos therapy. Together, exosome therapy has high clinical value and application prospects, both in its role and in combination with biomaterials, while novel drugs or molecules loaded into exosomes as carriers targeting wound cells will be development trends.
Do different exosome biogenesis pathways and selective cargo enrichment contribute to exosomal heterogeneity?
Exosomes are emerging intercellular communicators essential for cellular homeostasis during development and differentiation. The dysregulation in exosome-mediated communication alters cellular networking leads to developmental defects and chronic diseases. Exosomes are heterogeneous in nature depending on differences in size, membrane protein abundance, and differential cargo load. In this review, we have highlighted the latest developments in exosome biogenesis pathways, heterogeneity, and selective enrichment of various exosomal cargoes including proteins, nucleic acids, and mitochondrial DNA. Furthermore, the recent developments in the isolation techniques of exosome subpopulations have also been discussed. The comprehensive knowledge of extracellular vesicle heterogeneity and selective cargo enrichment during specific pathology may provide a clue for disease severity and early prognosis possibilities. The release of specific exosome subtypes is associated with the progression of specific disease type and hence a probable tool for therapeutics and biomarker development. This article is protected by copyright. All rights reserved.
Harnessing cancer stem cell-derived exosomes to improve cancer therapy
Cancer stem cells (CSCs) are the key “seeds” for tumor initiation and development, metastasis, and recurrence. Because of the function of CSCs in tumor development and progression, research in this field has intensified and CSCs are viewed as a new therapeutic target. Exosomes carrying a wide range of DNA, RNA, lipids, metabolites, and cytosolic and cell-surface proteins are released outside of the originating cells through the fusion of multivesicular endosomes or multivesicular bodies with the plasma membrane. It has become evident that CSC‐derived exosomes play a significant role in almost all “hallmarks” of cancer. For example, exosomes from CSCs can maintain a steady state of self-renewal in the tumor microenvironment and regulate microenvironmental cells or distant cells to help cancer cells escape immune surveillance and induce immune tolerance. However, the function and therapeutic value of CSC‐derived exosomes and the underlying molecular mechanisms are still largely undefined. To provide an overview of the possible role of CSC‐derived exosomes and targeting strategies, we summarize relevant research progress, highlight the potential impact of detecting or targeting CSC‐derived exosomes on cancer treatment, and discuss opportunities and challenges based on our experience and insights in this research area. A more thorough understanding of the characteristics and function of CSC‐derived exosomes may open new avenues to the development of new clinical diagnostic/prognostic tools and therapies to prevent tumor resistance and relapse.
Exosomes from Human Umbilical Cord Mesenchymal Stem Cells Facilitates Injured Endometrial Restoring in Early Repair Period through miR-202-3p Mediating Formation of ECM
Abstract
Endometrial damage repair disorder is the main reason of intrauterine adhesions (IUA) and thin endometrium (TA), which is caused by curettage or infection. Exosomal miRNAs derived from human umbilical cord mesenchymal stem cells (hucMSCs) were reported to play an important role in damage repair disorder, including endometrial fibrosis. In this study, we aimed to investigate the role of hucMSCs-derived exosomal microRNA-202-3p (miR-202-3p) in endometrial damage repair. We established rat endometrial injury model according to curettage to mimic women curettage abortion operation. The miRNA array analysis indicated that miR-202-3p was increased and matrix metallopeptidase 11 (MMP11) was decreased in the exosomes-treated rat uterine tissues. Bioinformatics analysis suggested that MMP11 is the target gene of miR-202-3p. We observed that the mRNA and protein of MMP11 were significantly decreased in exosome treatment group on day 3, and the components of extracellular matrix (ECM) COL1A1, COL3A1, COLVI and fibronectin (FN) protein were increased. And we found that when the injured human stromal cells were treated with miR-202-3p overexpression exosomes, the COLVI and FN were also upregulated in protein and mRNA expression level. For the first time MMP11 was proved to be the target gene of miR-202-3p by dual luciferase reporter system. At last, we found the state of stromal cells was better in miR-202-3p overexpression exosomes group compared to exosomes group, and miR-202-3p overexpression exosomes markedly upregulated the FN and collagen on day 3 after endometrial injury. We thought that miR-202-3p overexpression exosomes promoted endometrial repair by regulating ECM remodeling in early repair of damaged endometrium. Taken together, these experimental findings may provide a theoretical basis for understanding endometrial repair and an insight into the clinical treatment for IUA. Human umbilical cord mesenchymal stem cells exosomal miR-202-3p could regulate the expression of MMP11 and promote the accumulation of extracellular matrix, such as COL1A1, COL3A1, COLVI, FN, in the early repair period of endometrial injury.
Exosome Therapy: An Emerging Research Area in Regenerative Medicine (2023)
Stem cell therapy, a rapidly advancing field in regenerative medicine, has shown immense potential in treating a range of degenerative diseases. This therapeutic approach primarily involves the use of adult stem cells, often sourced from umbilical cord tissue, bone marrow or adipose tissue, to repair damaged or diseased tissues in the body. A particular focus has been on human mesenchymal stem cells (hMSCs), which have demonstrated significant regenerative capabilities.