The Protein Content of Extracellular Vesicles Derived from Expanded Human Umbilical Cord Blood-Derived CD133+ and Human Bone Marrow-Derived Mesenchymal Stem Cells Partially Explains Why both Sources are Advantageous for Regenerative Medicine

Abstract

Adult stem cells have beneficial effects when exposed to damaged tissue due, at least in part, to their paracrine activity, which includes soluble factors and extracellular vesicles (EVs). Given the multiplicity of signals carried by these vesicles through the horizontal transfer of functional molecules, human mesenchymal stem cell (hMSCs) and CD133 cell-derived EVs have been tested in various disease models and shown to recover damaged tissues. In this study, we profiled the protein content of EVs derived from expanded human CD133 cells and bone marrow-derived hMSCs with the intention of better understanding the functions performed by these vesicles/cells and delineating the most appropriate use of each EV in future therapeutic procedures. Using LC-MS/MS analysis, we identified 623 proteins for expanded CD133-EVs and 797 proteins for hMSCs-EVs. Although the EVs from both origins were qualitatively similar, when protein abundance was considered, hMSCs-EVs and CD133-EVs were different. Gene Ontology (GO) enrichment analysis in CD133-EVs revealed proteins involved in a variety of angiogenesis-related functions as well proteins related to the cytoskeleton and highly implicated in cell motility and cellular activation. In contrast, when overrepresented proteins in hMSCs-EVs were analyzed, a GO cluster of immune response-related genes involved with immune response-regulating factors acting on phagocytosis and innate immunity was identified. Together our data demonstrate that from the point of view of protein content, expanded CD133-EVs and hMSCs-EVs are in part similar but also sufficiently different to reflect the main beneficial paracrine effects widely reported in pre-clinical studies using expanded CD133 cells and/or hBM-MSCs.

Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia‐reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response

“…Therefore, we hypothesized that huc-MSC-EVs are rich in antioxidant proteins. Lots of antioxidant enzymes that regulated the redox status had been found enriched in MSC-EVs, including catalase, SOD1, SOD2, glutathione peroxidase, and others (49). Moreover, Yan et al (32) demonstrated that the specific antioxidant enzyme glutathione peroxidase 1 in huc-MSC exosomes was required for the recovery of hepatic oxidant injury.…”

“…To evaluate the underlying mechanisms, we analyzed the publicly available database. Interestingly, Angulski et al (49) showed that MnSOD, which is mainly located in mitochondrial components, was found in bone marrow (BM)-MSC-EVs using liquid chromatographytandem mass spectrometry analysis, suggesting that MnSOD might have a specific function (Fig. 6A).…”

Static Magnetic Field (SMF) as a Regulator of Stem Cell Fate – New Perspectives in Regenerative Medicine Arising from an Underestimated Tool

“…Recently, special attention has been paid to stem cell-derived microvesicles (MVs), which transport a wide range of cargo including proteins, organelles, RNA, miRNA and bioactive lipids [ 24 , 25 ]. MVs are enriched in bioactive molecules, thus they play a pivotal role in many biological processes, including tissue regeneration.…”

A New Approach to Cerebral Palsy Treatment: Discussion of the Effective Components of Umbilical Cord Blood and its Mechanisms of Action

“…for better understanding of the functions in each vesicle type and delineating the appropriate use of each EV in therapeutic procedures 59 . For protein content, expanded CD133þ-EVs might be better inducers or modulators of angiogenesis (e.g.…”