Remodeled CD146⁺CD271⁺ Bone Marrow Mesenchymal Stem Cells from Patients with Polycythemia Vera Exhibit Altered...

An essential component of the hematopoietic microenvironment, bone marrow mesenchymal stem cells (BM-MSCs) play an important role in the homeostasis and pathogenesis of the hematopoietic system by regulating the fate of hematopoietic stem cells (HSCs). Previous studies revealed that BM-MSCs were functionally remodeled by malignant cells in leukemia. However, the alterations in BM-MSCs in polycythemia vera (PV) and their effects on HSCs still need to be elucidated. Our results demonstrated that although BM-MSCs from PV patients shared similar surface markers with those from healthy donors, they exhibited enhanced proliferation, decreased senescence, and abnormal osteogenic differentiation capacities. The CD146⁺CD271⁺ BM-MSC subpopulation, which is considered to give rise to typical cultured BM-MSCs and form bone and the hematopoietic stroma, was then sorted. Compared with those from healthy donors, CD146⁺CD271⁺ BM-MSCs from PV patients showed an impaired mesensphere formation capacity and abnormal differentiation toward osteogenic lineages. In addition, CD146⁺CD271⁺ PV BM-MSCs showed altered hematopoietic supportive activity when cocultured with cord blood CD34⁺ cells. Our study suggested that remodeled CD146⁺CD271⁺ BM-MSCs might contribute to the pathogenesis of PV, a finding that will shed light on potential therapeutic strategies for PV.