Eltrombopag restores proliferative capacity and adipose-osteogenic balance of mesenchymal stromal cells in low-risk myelodysplastic syndromes

Abstract

In low-risk myelodysplastic syndromes (MDS), the proinflammatory signaling is excessive, and the proliferation and differentiation potentials of mesenchymal stromal cells (MSCs) are strongly impaired. Eltrombopag (ELT) has been demonstrated recently effective and relatively safe in low-risk MDS with severe thrombocytopenia. However, its impact on the MDS-MSCs has not been investigated in any detail. Here, for the first time, we investigated the changes induced by ELT in MSCs’ viability, proliferation, apoptosis, senescence, multilineage differentiation properties, and stem cell support capacity in low-risk MDS patients. We demonstrated that ELT may act on improving the impaired inflammatory profile and reactivating the downregulated canonical WNT signaling pathway in low-risk MDS, and also restoring the self-renewal capacity and the balance in adipose-osteogenic differentiation of MDS-MSCs.