Adipose Tissue-Derived Stem Cell Extracellular Vesicles Suppress Glioblastoma Proliferation, Invasiveness and Angiogenesis

Abstract

Extracellular vesicles (EVs) are attractive anticancer drug delivery candidates as they confer several fundamental properties, such as low immunogenicity and the ability to cross biological barriers. Mesenchymal stem cells (MSCs) are convenient producers for high EV yields, and patient-derived adipose tissue MSC-EVs could serve as personalised carriers. However, MSC-EV applications raise critical concerns as their natural cargo can affect tumour progression in both inducing and suppressing ways. In this study, we investigated the effect of adipose tissue-derived mesenchymal stem cell EVs (ASC-EVs) on several glioblastoma (GBM) cell lines to define their applicability for anticancer therapies. ASC-EVs were isolated from a cell-conditioned medium and characterised by size and specific markers. The internalisation of fluorescently labelled ASC-EVs by human GBM cells HROG36, U87 MG, and T98G was evaluated by fluorescent microscopy. Changes in GBM cell proliferation after ASC-EV application were determined by the metabolic PrestoBlue assay. Expression alterations in genes responsible for cell adhesion, proliferation, migration, and angiogenesis were evaluated by quantitative real-time PCR. ASC-EV effects on tumour invasiveness and neoangiogenesis in ovo were analysed on the chicken embryo chorioallantoic membrane model (CAM). ASC-EV treatment reduced GBM proliferation in vitro and significantly downregulated invasiveness-related genes ITGα5 (in T98G and HROG63) and ITGβ3 (in HROG36) and the vascularisation-inducing gene KDR (in all GBM lines). Additionally, an approximate 65% reduction in the GBM invasion rate was observed in CAM after ASC-EV treatment. Our study indicates that ASC-EVs possess antitumour properties, reducing GBM cell proliferation and invasiveness, and can be applied as anticancer therapeutics and medicine carriers.

Experimental Tumor Induction and Evaluation of Its Treatment in the Chicken Embryo Chorioallantoic Membrane Model: A Systematic Review

“…The second phase consisted of questions about CAM methodology, results, discussion, and conclusions. The articles were classified according to the score obtained: low quality (score 0-5), medium quality (score 6-15), and high quality (score [16][17][18][19][20]. Following this quality study, 6 articles were excluded (Figure 1), and 74 articles were included and are analyzed in Tables 1-5.…”

“…In half of the studies analyzed (55%), tumor establishment was established with Matrigel, although culture medium (18%) and PBS (9%) were also used. However, other matrices are also used to establish tumor growth, as in the case of Gečys et al (2023), who used rat tail collagen as the matrix for cell inoculation [16], or Yart et al (2022), who used Geltrex [22]. On the other hand, it should be noted that only 9% of the studies used a silicone ring in the CAM to infiltrate the tumor cells into the CAM and facilitate its establishment at a fixed point, preventing its spread through the CAM (Figure 4D).…”

Mesenchymal stem/stromal cells- a principal element for tumour microenvironment heterogeneity

“…It has been demonstrated that CCL5 secreted by ADMSCs can induce PD-L1 expression in breast cancer cells ( 61 ). Exosomes derived from ADMSCs reduce glioblastoma proliferation and significantly down-regulate the invasion-related genes ITGα5 and ITGβ3, as well as the angiogenesis induction gene KDR ( 62 ).…”

Roles of adipose-derived stem cells and derived exosomes in therapeutic applications to testicular injury caused by cisplatin

“…ADSCs have the ability to differentiate into multiple cell types, including adipocytes, osteoblasts, chondrocytes, and myocytes [ 4 ]. In addition, ADSCs secrete various growth factors and cytokines that promote tissue repair and regeneration [ 5 , 6 ]. Exosomes are small membrane-bound vesicles that can transport proteins, nucleic acids, and other molecules between cells [ 7 ].…”

“…In recent years, ADSCs and ADSC-Ex have been investigated for their therapeutic potential in various diseases and conditions, including wound healing, tissue regeneration, autoimmune diseases, and neurological disorders [6,11]. In preclinical studies, ADSCs and adipose-derived mesenchymal stem cell extracellular vesicles (ADSC-EVs) have shown promising results in improving tissue function and reducing inflammation in animal models of these diseases [12].…”