Remodeled CD146 + CD271 + Bone Marrow Mesenchymal Stem Cells from Patients with Polycythemia Vera Exhibit Altered Hematopoietic Supportive Activity
Stem cell reviews and reports(2022)
摘要
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. Graphical abstract
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关键词
Bone marrow mesenchymal stem cells,CD146+CD271+,Hematopoietic niche,Polycythemia vera
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