Abstract

Adult Mesenchymal stem cells-derived exosomes carry several biologically active molecules that play prominent roles in controlling disease manifestations. The content of these exosomes, their functions, and effect on the immune cells may differ depending on their tissue sources. Therefore, in this study, we purified the exosomes from three different sources and, using the RNA-Seq approach, highly abundant microRNAs were identified and compared between exosomes and parental cells. The effects of exosomes on different immune cells were studied in vitro by incubating exosomes with PBMC and neutrophils and assessing their functions. The expression levels of several miRNAs varied within the different MSCs and exosomes. Additionally, the expression profile of most of the miRNAs was not similar to that of their respective sources. Exosomes isolated from different sources had different abilities to induce the process of neurogenesis and angiogenesis. Moreover, these exosomes demonstrated their varying effect on PBMC proliferation, neutrophil survival, and NET formation, highlighting their versatility and broad interaction with immune cells. The knowledge gained from this study will improve our understanding of the miRNA landscape of exosomes from hMSCs and provide a resource for further improving our understanding of exosome cargo and their interaction with immune cells.

Highlights

  • Human mesenchymal stem cells are widely recognized for their regenerative nature and studied as therapeutic modalities in many chronic and inflammatory diseases.They are multilineage progenitor cells, well known for their distinct role in repair, regenerative mechanisms [1,2,3], and regulating immune responses [4,5,6]

  • The cryopreserved Human Mesenchymal Stem cells (hMSC) isolated from bone marrow, Wharton jelly, and adipose tissue of adult donors (18–50 years old) were revived and cultured for expansion (Table S1)

  • The hMSCs were visualized using Phase-contrast microscopy, which revealed the spindle-shaped morphology of tissue-specific hMSCs (Figure 1A)

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Summary

Introduction

Human mesenchymal stem cells (hMSCs) are widely recognized for their regenerative nature and studied as therapeutic modalities in many chronic and inflammatory diseases. They are multilineage progenitor cells, well known for their distinct role in repair, regenerative mechanisms [1,2,3], and regulating immune responses [4,5,6]. Most of the properties of hMSCs can be recapitulated through a particular class of extracellular vesicles called exosomes [8]. Exosomes are vesicles of endocytic origin with a size range between 30–150 nm [9].

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