Mesenchymal stem cell abnormalities in patients with multiple myeloma

Abstract

Osteolytic bone lesions are common in patients with multiple myeloma (MM), a clonal plasma cell disorder, and result from increased osteoclastic bone resorption and decreased osteoblastic bone formation. Because mesenchymal stem cells (MSCs) are committed towards cells of the osteoblast lineage, we compared the in vitro characteristics of MSCs from the bone marrow of 18 MM patients (MM-MSCs) and eight normal donors (ND-MSCs). MM-MSCs displayed deficient growth that could be explained in part by the reduced expression of several growth factor receptors on the surface of MM-MSCs compared with ND-MSCs. Receptor downregulation was observed on RT-PCR analysis. A major finding was an approximately fivefold higher expression of osteoblast inhibitor DKK1 at transcript and protein levels in MM-MSCs than ND-MSCs. These data suggest that defective osteoblast function in patients with advanced MM may be related not only to factors released by tumor myeloma cells but also to MSC abnormalities.