We have collected the most exciting new researches in the field of genetics and cellular research in the past week.
Exosomes from adipose-derived stem cells accelerate wound healing by increasing the release of IL-33 from macrophages
Background
Mesenchymal stem cell (MSC) -derived exosomes, especially adipose-derived mesenchymal stem cell exosomes (ADSC-Exos), have emerged as a promising alternative for skin damage repair with anti-inflammatory, angiogenic and cell proliferation effects while overcoming some of the limitations of MSC. However, the mechanism by which ADSC-Exos regulates inflammatory cells during wound healing remains unclear. This study investigated how ADSC-Exos regulate macrophages to promote wound healing.
Methods
ADSC-Exos were isolated using ultracentrifugation, with subsequent quantification of exosomes particle number. To investigate their role in wound healing, the effects of ADSC-Exos on inflammation, angiogenesis, collagen deposition and macrophage polarization were evaluated through immunohistochemical staining, immunofluorescence and western blotting. Changes in gene expression associated with ADSC-Exos-induced macrophage polarization were analyzed using qPCR. RNA sequencing was performed to identify differentially expressed genes affected by ADSC-Exos. The critical role of IL-33 in the wound healing process was further confirmed using Il33−/− mice. Additionally, co-culture experiments were conducted to explore the effects of IL-33 on keratinocyte proliferation, collagen deposition and epithelialization.
Results
ADSC-Exos inhibited the expression of TNF-α and IL-6, induced M2 macrophage polarization, promoted collagen deposition and angiogenesis, and accelerated wound healing. RNA sequencing identified IL-33 as a key mediator in this process. In Il33−/− mice, impaired wound healing and decreased M2 macrophage polarization were observed. The co-culture experiments showed that IL-33 enhanced keratinocyte function through activation of the Wnt/β-catenin signaling pathway. These findings highlight the therapeutic potential of ADSC-Exos in wound healing by modulating IL-33.
Conclusions
ADSC-Exos promote wound healing by regulating macrophage polarization and enhancing IL-33 release which drives keratinocyte proliferation, collagen deposition and epithelialization via the Wnt/β-catenin signaling pathway. These findings provide a mechanistic basis for the therapeutic potential of ADSC-Exos in tissue repair and regeneration.
Bibliometric and Visualization Analysis of Research on Exosomes as Drug Delivery Systems (2008-2023)
Objective: Exosomes are unique bio-nanomaterials possessing significant value and potential for drug delivery systems. However, to date, no bibliometric studies in this field have been reported. Our aim is to explore the research hotspots and trends of exosome drug-carrying systems across various medical fields through bibliometric analyses.
Methods: Articles and reviews related to "exosome" and "drug delivery" are retrieved from the Web of Science Core Collection. VOSviewer, CiteSpace, Scimago Graphica, and Origin 2021 are employed for bibliometric analyses.
Results: A total of 771 articles from 60 countries, such as China and the United States, are included. The number of papers concerning exosomal drug delivery systems has been increasing yearly. The main research institutions are the Chinese Academy of Sciences, Shanghai Jiao Tong University, Huazhong University of Science and Technology, Fudan University, and Sichuan University. The Journal of Controlled Release is the most prevalent and frequently cited journal in this field. These papers are authored by 247 individuals, with Ando, Hidenori having the highest number of publications and Alvarez-Erviti L receiving the most citations. "Extracellular vesicles", "drug delivery", "in vitro", "nanoparticles", "cells", "delivery", and "mesenchymal stem cells" are the principal keywords for this hotspot.
Conclusion: This pioneering bibliometric study offers a comprehensive overview of the research trends and advancements in exosomal drug delivery systems in medicine over the past fifteen years.
Adapted Exosomes for Addressing Chemotherapy-induced Premature Ovarian Insufficiency
Background
Premature ovarian insufficiency (POI) presents a multifaceted challenge with limited treatment options. This study explored the therapeutic potential of exosome-based interventions for chemotherapy-induced POI.
Methods
Adapted exosomes were engineered from umbilical cord mesenchymal stem cells (UC-MSCs) under a specific co-culture system and used for treating in vitro and in vivo models of chemotherapy-induced premature ovarian insufficiency.
Results
In vitro models revealed the significant impact of adapted exosomes, which promoted granulosa cell proliferation, decrease apoptosis, and enhanced ovarian functional markers. The findings in an in vivo chemotherapy-induced POI mouse model indicated the restoration of ovarian morphology, follicle numbers, and fertility in both the naïve and adapted exosome-treated groups. Notably, the adapted exosome group demonstrated a heightened pregnancy rate, increased numbers of primary follicles, and a significant reduction in ovarian apoptosis. MiRNA profiling revealed distinctive cargo in the adapted exosomes, among which miR-20b-5p played a pivotal role in regulating apoptosis and inflammation; this finding is especially important given that apoptosis is one of the primary complications of chemotherapy-induced POI. Furthermore, cells treated with adapted exosomes demonstrated significant overexpression of miR-20b-5p, resulting in decreased PTEN expression and the activation of the PI3K-AKT pathway—a crucial mechanism in mitigating chemotherapy-induced POI.
Conclusions
This study introduces an exosome-based therapeutic approach, emphasizing the importance of exosome cargo composition in treating disorders. Further investigation into the identified miRNA profile in adapted exosomes is necessary to clarify the underlying mechanisms, potentially leading to the development of a new treatment for clinical premature ovarian insufficiency.