The Osteoblastogenesis Potential of Adipose Mesenchymal Stem Cells in Myeloma Patients Who Had Received Intensive Therapy

Multiple myeloma (MM) is characterized by advanced osteolytic lesions resulting from the activation of osteoclasts (OCs) and inhibition of osteoblasts (OBs). OBs are derived from mesenchymal stem cells (MSCs) from the bone marrow (BM), however the pool and function of BMMSCs in MM patients (MM-BMMSCs) are reduced by myeloma cells (MCs) and cytokines secreted from MCs and related anti-MM treatment. Such reduction in MM-BMMSCs currently cannot be restored by any means. Recently, genetic aberrations of MM-BMMSCs have been noted, which further impaired their differentiation toward OBs. We hypothesize that the MSCs derived from adipose tissue (ADMSCs) can be used as alternative MSC sources to enhance the pool and function of OBs. Therefore, the purpose of this study was to compare the osteogenesis ability of paired ADMSCs and BMMSCs in MM patients who had completed intensive therapy. Fifteen MM patients who had received bortezomib-based induction and autologous transplantation were enrolled. At the third month after the transplant, the paired ADMSCs and BMMSCs were obtained and cultured. Compared with the BMMSCs, the ADMSCs exhibited a significantly higher expansion capacity (100% vs 13%, respectively; P = .001) and shorter doubling time (28 hours vs 115 hours, respectively; P = .019). After inducing osteogenic differentiation, although the ALP activity did not differ between the ADMSCs and BMMSCs (0.78 U/µg vs 0.74±0.14 U/µg, respectively; P = .834), the ADMSCs still exhibited higher calcium mineralization, which was determined using Alizarin red S (1029 nmole vs 341 nmole, respectively; P = .001) and von Kossa staining (2.6 E+05 µm2 vs 5 E+04 µm2, respectively; P = .042), than the BMMSCs did. Our results suggested that ADMSCs are a feasible MSC source for enhancing the pool and function of OBs in MM patients who have received intensive therapy.