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Weekly Exosomes Digest (4/4 March 2024)

We have collected the most exciting new researches in the field of genetics and cellular research in the past week.





Human Exosomes Harvested from Stem Cells in Urine Produce Rejuvenation in Mice


Exosomes are a class of extracellular vesicle, membrane-wrapped packages of molecules that carry a sizable fraction of the chemical communications that takes place between cells. The various types of extracellular vesicle are presently ordered in a taxonomy by their size rather than any more subtle combination of features. Those subtle features definitely exist; exosomes from different cell types and different environmental circumstances are quite different from one another in any number of ways. The present taxonomy of extracellular vesicles is indicative of a lack of detailed understanding regarding (a) the mechanisms determining formation of extracellular vesicles, as well as (b) the factors determining the contents of extracellular vesicles.




Exciting Exosomes in Aesthetic Dermatology


Exosomes are extracellular vesicles produced by all cell types. They are spherical structures 30 to 160 nm in diameter composed of a lipid bilayer encapsulating a variety of biologically active substances including messenger RNA, micro RNA, DNA, proteins, and lipids. They were discovered in 1983 and thought to represent a form of cellular waste disposal. The term “exosome” was coined in 1987 when it was recognized that exosomes represented a form of intercellular communication and a method of macromolecule transmission among cells. Here are answers to the most common questions about exosomes.




Why a New Inhalable Lung Cancer Treatment Is So Promising


Cells in the human body chat with each other all the time. One major way they communicate is by releasing tiny spheres called exosomes. These carry fats, proteins, and genetic material that help regulate everything from pregnancy and immune responses to heart health and kidney function.

Now, a new Columbia University study in Nature Nanotechnology demonstrated that these "nanobubbles" can deliver potent immunotherapy directly to tough-to-treat lung cancer tumors via inhalation.

"Exosomes work like text messages between cells , sending and receiving information," said lead researcher Ke Cheng, PhD, professor of biomedical engineering at Columbia. "The significance of this study is that exosomes can bring mRNA-based treatment to lung cancer cells locally, unlike systemic chemotherapy that can have side effects throughout the body. And inhalation is totally noninvasive. You don't need a nurse to use an IV needle to pierce your skin."

Cheng expects a human trial could launch within 5 years. For now, his study is attracting attention because it marks an advance in three areas of intense interest by researchers and biotech companies alike: Therapeutic uses of exosomes, inhalable treatments for lung conditions, and the safe delivery of powerful interleukin-12 (IL-12) immunotherapy.



Airway basal cell‑derived exosomes suppress epithelial‑mesenchymal transition of lung cells by inhibiting the expression of ANO1


Disruption of the epithelial‑mesenchymal transition (EMT) of activated lung cells is an important strategy to inhibit the progression of idiopathic pulmonary fibrosis (IPF). The present study investigated the role of exosomes derived from airway basal cells on EMT of lung cells and elucidate the underlying mechanism. Exosomes were characterized by nanoparticle tracking analysis, transmission electron microscopy imaging and markers detection. The role of exosome on the EMT of lung epithelial cells and lung fibroblasts induced by TGF‑β1 was detected. RNA sequencing screened dysregulated genes in exosome‑treated group, followed by the bioinformatical analysis. One of the candidates, anoctamin‑1 (ANO1), was selected for further gain‑and‑loss phenotype assays. A bleomycin‑induced pulmonary fibrosis model was used to evaluate the treatment effect of exosomes. Exosomes were round‑like and positively expressed CD63 and tumor susceptibility gene 101 protein. Treatment with exosomes inhibited the EMT of lung cells activated by TGF‑β1. 4158 dysregulated genes were identified in exosome‑treated group under the threshold of |log2 fold‑change| value >1 and they were involved in the metabolism of various molecules, as well as motility‑related biological processes. A key gene, ANO1, was verified by reverse transcription‑quantitative PCR, whose overexpression induced the EMT of lung cells. By contrast, ANO1 knockdown reversed the EMT induced by TGF‑β1. In vivo assay indicated that exosome treatment ameliorated pulmonary fibrosis and inhibited the upregulation of ANO1 induced by bleomycin. In conclusion, airway basal cell‑derived exosomes suppressed the EMT of lung cells via the downregulation of ANO1. These exosomes represent a potential therapeutic option for patients with IPF.




Identification of potential biomarkers for aging diagnosis of mesenchymal stem cells derived from the aged donors


Background

The clinical application of human bone-marrow derived mesenchymal stem cells (MSCs) for the treatment of refractory diseases has achieved remarkable results. However, there is a need for a systematic evaluation of the quality and safety of MSCs sourced from donors. In this study, we sought to assess one potential factor that might impact quality, namely the age of the donor.


Methods

We downloaded two data sets from each of two Gene Expression Omnibus (GEO), GSE39035 and GSE97311 databases, namely samples form young (< 65 years of age) and old (> 65) donor groups. Through, bioinformatics analysis and experimental validation to these retrieved data, we found that MSCs derived from aged donors can lead to differential expression of gene profiles compared with those from young donors, and potentially affect the function of MSCs, and may even induce malignant tumors.


Results

We identified a total of 337 differentially expressed genes (DEGs), including two upregulated and eight downregulated genes from the databases of both GSE39035 and GSE97311. We further identified 13 hub genes. Six of them, TBX15, IGF1, GATA2, PITX2, SNAI1 and VCAN, were highly expressed in many human malignancies in Human Protein Atlas database. In the MSCs in vitro senescent cell model, qPCR analysis validated that all six hub genes were highly expressed in senescent MSCs. Our findings confirm that aged donors of MSCs have a significant effect on gene expression profiles. The MSCs from old donors have the potential to cause a variety of malignancies. These TBX15, IGF1, GATA2, PITX2, SNAI1, VCAN genes could be used as potential biomarkers to diagnosis aging state of donor MSCs, and evaluate whether MSCs derived from an aged donor could be used for therapy in the clinic. Our findings provide a diagnostic basis for the clinical use of MSCs to treat a variety of diseases.


Conclusions

Therefore, our findings not only provide guidance for the safe and standardized use of MSCs in the clinic for the treatment of various diseases, but also provide insights into the use of cell regeneration approaches to reverse aging and support rejuvenation.



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