Different Donors Mesenchymal Stromal Cells Secretomes Reveal Heterogeneous Profile of Relevance for Therapeutic Use

Abstract

Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder caused by null mutations in the dystrophin gene. Although the primary defect is the deficiency of muscle dystrophin, secondary events, including chronic inflammation, fibrosis, and muscle regeneration failure are thought to actively contribute to disease progression. Despite several advances, there is still no effective therapy for DMD. Therefore, the potential regenerative capacities, and immune-privileged properties of mesenchymal stromal cells (MSCs), have been the focus of intense investigation in different animal models aiming the treatment of these disorders. However, these studies have shown different outcomes according to the sources from which MSCs were obtained, which raise the question whether stem cells from distinct sources have comparable clinical effects. Here, we analyzed the protein content of the secretome of MSCs, isolated from three different sources (adipose tissue, skeletal muscle, and uterine tubes), obtained from five donors and evaluated their in vitro properties when cocultured with DMD myoblasts. All MSC lineages showed pathways enrichment related to protein metabolic process, oxidation-reduction process, cell proliferation, and regulation of apoptosis. We found that MSCs secretome proteins and their effect in vitro vary significantly according to the tissue and donors, including opposite effects in apoptosis assay, indicating the importance of characterizing MSC secretome profile before its use in animal and clinical trials. Despite the individual differences a pool of conditioned media from all MSCs lineages was able to delay apoptosis and enhance migration when in contact with DMD myoblasts.

Persistence of fluorescent nanoparticle‐labeled bone marrow mesenchymal stem cells in vitro and after intra‐articular injection

“…Whether this was due to an effect of QDs or to drift of MSC immunophenotype over the passages in separate cultures is not clear, and further studies are needed in this area. Although molecular markers continue to be used to characterize stem cell populations, recent studies with human MSCs indicate that cells isolated from different donors (Szepesi et al, ) or from different sites from the same donor (Hatakeyama et al, ; Sacchetti et al, ) and cells treated with different enzymatic digestion methods for detachment (Tsuji et al, ) can have different surface antigen expression and even MSCs with identical cell surface phenotype from different tissues and donors have distinct transcriptomic signatures and differentiation capacities, likely due to the broad overlap of cells with MSC markers with other cell populations (Assoni, Coatti, Valadares, et al, ; Sacchetti et al, ). Thus, the immunophenotypic characterization of MSCs remains unclear, and MSCs are currently best defined functionally.…”

Deepening a Simple Question: Can MSCs Be Used to Treat Cancer?

“…In the latter case, potency tests should also be developed to discriminate MSCs populations with the appropriate activity for a desirable anti-tumor effect. It has been observed that MSCs secrete different proteins even when they are obtained from the same tissue of different donors or from different tissues of the same donor (158). Additionally, MSCs activity is known to decline with donor's age (159).…”

Mesenchymal stromal cell‐derived extracellular vesicles as cell‐free biologics for the ex vivo expansion of hematopoietic stem cells

“…Another study revealed that altered cell migration resulting from changes in MSC surface markers during prolonged cultivation could significantly reduce MSC homing ability (Jung et al, 2011). Though MSCs isolated from multiple sources share similar phenotypic characteristics, there have been proven differences in therapeutic potential based upon their origin (Vieira et al, 2010; Eiro et al, 2014; Assoni et al, 2017).…”