Comprehensive proteomic analysis of exosomes derived from human bone marrow, adipose tissue, and umbilical cord mesenchy

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RESEARCH

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Comprehensive proteomic analysis of exosomes derived from human bone marrow, adipose tissue, and umbilical cord mesenchymal stem cells Zheng-gang Wang , Zhi-yi He, Shuang Liang, Qing Yang, Peng Cheng* and An-min Chen*

Abstract Background: Mesenchymal stem cell (MSC)-derived exosomes have shown comprehensive application prospects over the years. Despite performing similar functions, exosomes from different origins present heterogeneous characteristics and components; however, the relative study remains scarce. Lacking of a valuable reference, researchers select source cells for exosome studies mainly based on accessibility and personal preference. Methods: In this study, exosomes secreted by MSCs derived from different tissues were isolated, by ultracentrifugation, and proteomics analysis was performed. A total of 1014 proteins were detected using a label-free method. Results: Bioinformatics analysis revealed their shared function in the extracellular matrix receptor. Bone marrow MSCderived exosomes showed superior regeneration ability, and adipose tissue MSC-derived exosomes played a significant role in immune regulation, whereas umbilical cord MSC-derived exosomes were more prominent in tissue damage repair. Conclusions: This study systematically and comprehensively analyzes the human MSC-derived exosomes via proteomics, which reveals their potential applications in different fields, so as to provide a reference for researchers to select optimal source cells in future exosome-related studies. Keywords: Mesenchymal stem cells, Exosomes, Proteomics, Extracellular vesicles, Stem cell-based therapy

Background In recent years, mesenchymal stem cells (MSCs) have been widely used in clinical treatment owing to their multi-differentiation potential [1, 2]. These cells play a significant role in immune regulation [3] and angiogenesis [4], especially in the heart, bone, cartilage, nerves, and skin [5–7]. There are many tissue-derived MSCs that have been used in therapeutic research, such as the bone marrow (BM), adipose tissue (AT), fetal lung, dental pulp, and umbilical cord (UC) [8, 9]. Paracrine secretion, * Correspondence: [email protected]; [email protected] Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province 430030, People’s Republic of China

particularly exosomes, is one of the main mechanisms of therapeutic action of MSCs [10], which has received much attention for its important roles in cellular communication and regenerative medicine. Exosomes are lipid bilayer vesicles of 30–200 nm in diameter originating from endocytosis [11], which are secreted by multiple cells and appear in the supernatant of cell cultures or body fluids, such as the blood, saliva, urine, breast milk, cerebrospinal fluid, bile, and lymph [11–13]. Many types of molecules, including proteins, lipids, and nucleic acids, are present in exosomes [11]. When exosomes are absorbed by other cells, these molecules are transferr