iPSC-derived osteoclasts: “A new tool to study multiple myeloma induced osteolysis”
Multiple myeloma (MM) is the second most common hematological malignancy in adults characterized by clonal proliferation of plasma cells. The increased life expectancy by the use of novel therapeutic drugs has revealed the impact of secondary cancer-induced pathologies. More specifically, up to 90% of MM patients develop cancer-induced bone lesions, which has become a major cause of morbidity and mortality. Whereas an increase in osteoclast (OC) numbers and activity has been identified to be responsible for the osteolysis in MM, the mechanisms resulting from the OC and MM cell interactions are very poorly understood due to the difficulties in isolating and culturing primary OCs.
In this study, we used OCs derived from induced pluripotent stem cells (iPSCs) to model the bidirectional interactions between OCs and MM cells. We investigated the role of OCs on MM growth and drug resistance. In turn, the effect of MM cells on OC-mediated bone resorption was also evaluated.
We have generated OCs derived from iPSCs very efficiently. And iPSC-derived OCs showed to support MM cell growth and protect them from drug treatment such as melphalan and carfilzomib. In turn, MM cells can promote the OC-mediated bone resorption. Together, they form a vicious cycle to excerbate MM bone disease.
Collectively, we have demonstrated that iPSC-derived OCs resembled primary counterparts and can serve as an reliable platform to study the interactions between MM cells and OCs. The robustness to generate them from iPSCs, together with easy access to genetic manipulations makes this tool valuable in advancing the understanding of MM bone disease.