Role of Extracellular Vesicles from Adipose Tissue- and Bone Marrow-Mesenchymal Stromal Cells in Endothelial Proliferation and Chondrogenesis

Abstract

The secretome of mesenchymal stromal cells (MSCs) derived from different tissue sources is considered an innovative therapeutic tool for regenerative medicine.Although adipose tissue-and bone marrow-derived MSCs (ADSCs and BMSCs, respectively) share many biological features, the different tissue origins can be mirrored by variations in their secretory profile, and in particular in the secreted extracellular vesicles (EVs). In this study, we carried out a detailed and comparative characterization of middle-and small-sized EVs (mEVs and sEVs, respectively) released by either ADSCs or BMSCs. Their involvement in an endochondral ossification setting was investigated using ex vivo metatarsal culture models that allowed to explore both blood vessel sprouting and bone growth plate dynamics. Although EVs separated from both cell sources presented similar characteristics in terms of size, concentration, and marker expression, they exhibited different characteristics in terms of protein content and functional effects. ADSC-EVs overexpressed proangiogenic factors in comparison to the BMSC-counterpart, and, consequently, they were able to induce a significant increase in endothelial cord outgrowth. On the other hand, BMSC-EVs contained a higher amount of pro-differentiation and chemotactic proteins, and they were able to prompt growth plate organization. The present study highlights the importance of selecting the appropriate cell source of EVs for targeted therapeutic applications. K E Y W O R D S cartilage and bone development, ex vivo metatarsal culture model, extracellular vesicles, mesenchymal stromal cells, regenerative medicine Significance statement Mesenchymal stromal cells are a great source for regenerative medicine applications. Cells derived from different tissues might have distinctive characteristics. Many

An Overview of Current Research on Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Bibliometric Analysis From 2009 to 2021

“…Given the different types and abundance of proteins and RNAs in EVs derived from different MSCs, the selection of tissue-specific MSCs should be based on the pathological characteristics of diseases. According to available studies, ADSCs-derived EVs contained high levels of proangiogenic factors, BMSCs-derived EVs enriched with prodifferentiation and chemotactic proteins, and EVs secreted by hUCMSCs exhibited strong anti-inflammatory effects (Gorgun et al, 2021;Gupta et al, 2022). Therefore, further studies are warranted to elucidate the specific effects of different sources of MSC-EVs on various physiological processes and their strength, to guide application in disease therapy.…”

Intra-Articular Injection of Adipose-Derived Stem Cells Ameliorates Pain and Cartilage Anabolism/Catabolism in Osteoarthritis: Preclinical and Clinical Evidences

“…In vitro studies by co-culturing ADSCs and chondrocytes showed an increased secretion of many growth factors and cytokines, such as epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β), and bone morphogenetic protein 2 (BMP-2) of ADSCs, which in turn stimulated the synthesis of cartilage ECM ( Zhong et al, 2016 ). ADSCs-derived EVs contain functional proteins and RNAs, such as DKK-1, versican, annexin A1, and miR-100-5p, which could induce chondrogenesis and reduce inflammation ( Tofiño-Vian et al, 2018 ; Wu et al, 2019 ; Giannasi et al, 2020 ; Gorgun et al, 2021 ).…”

Regenerative and Anti-Inflammatory Potential of Regularly Fed, Starved Cells and Extracellular Vesicles In Vivo

“…EVs were separated from P3 regularly fed cells as follows: sub-confluent hBM-MSC cultured in SFM were washed three times in PBS and cultured in basal medium (αMEM, Gibco) for 72 h. Conditioned medium (CM) was harvested after 72 h and processed immediately through two subsequent centrifugation steps [ 33 ]. This clarified CM was differentially ultra-centrifuged (Optima XPN-100, Beckman-Coulter, Brea, CA, USA) at 10,000× g for 40 min at 4 °C and, subsequently, twice at 100,000× g for 2 h at 4 °C to pellet EVs [ 33 ]. EVs were resuspended in PBS and stored at −80 °C for further experiments or until in vivo injection.…”