PLoS One. 2014 Apr 10;9(4):e94395. doi: 10.1371/journal.pone.0094395.

The osteoblastogenesis potential of adipose mesenchymal stem cells in myeloma patients who had received intensive therapy.

Lin HH1, Hwang SM2, Wu SJ1, Hsu LF2, Liao YH3, Sheen YS3, Chuang WH1, Huang SY1.
  • 1Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
  • 2Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan.
  • 3Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan.

 

Abstract

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.

PMID: 24722177

 

Supplementary

The purpose of this study were to compare the osteogenesis potential of paired BMMSCs (bone marrow mesenchymal stem cells) and ADMSCs (adipose-derived mesenchymal stem cells) obtained from MM (multiple myeloma) patients who completed a bortezomib-based induction regimen followed by high-dose chemotherapy with autologous stem cell transplantation (HDT/AuSCT), a standard treatment for MM patients, and to determine whether ADMSCs are a suitable MSC source that can differentiate into adequate and functional OBs in MM patients.

Our data showed that the impaired osteoblastogenesis of MM-BMMSCs at post-intensive therapy resulted from the myeloma cells (MCs) and anti-MM therapy (Figure 1 and 2). However, MM-ADMSCs might not be affected by MCs and anti-MM treatment. Meanwhile, we confirmed that osteoblastogenesis can be induced in ADMSCs of MM patients who have received intensive treatment. This study displayed and supported that the ADMSCs are feasible and more favorable MSC source than BMMSCs for MM bone disease cell therapy in the future.

 

figure 1 15-0421Figure 1 Morphologies and Alizarin Red S staining of cultured ADMSCs and BMMSCs from two representative MM patients (Pt3 and Pt10). Both ADMSCs (d,j) and BMMSCs (a,g) had typical morphology for MSCs. Positive ARS staining for calcium deposits appeared red granules for ADMSCs (e,k) and paired BMMSCs (b,h).

 

 

figure 2 15-0421

Figure 2 The calcium deposition levels of cultured ADMSCs and BMMSCs for healthy donors, non-MM control and MM patients

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