Abstract
Multiple myeloma (MM) is an incurable B cell neoplasia characterized by the accumulation of tumor plasma cells within the bone marrow (BM). As a consequence, bone osteolytic lesions develop in 80% of patients and remain even after complete disease remission. We and others had demonstrated that BM-derived mesenchymal stromal cells (MSCs) are abnormal in MM and thus cannot be used for autologous treatment to repair bone damage. Adipose stromal cells (ASCs) represent an interesting alternative to MSCs for cellular therapy. Thus, in this study, we wondered whether they could be a good candidate in repairing MM bone lesions. For the first time, we present a transcriptomic, phenotypic, and functional comparison of ASCs from MM patients and healthy donors (HDs) relying on their autologous MSC counterparts. In contrast to MM MSCs, MM ASCs did not exhibit major abnormalities. However, the changes observed in MM ASCs and the supportive property of ASCs on MM cells question their putative and safety uses at an autologous or allogenic level.
Highlights
Multiple myeloma (MM) is a B cell neoplasia that accounts for approximately 1% of all cancers and 10% of hematologic neoplasias, with median age at diagnosis of about 70 years [1, 2]
Adipose stromal cells (ASCs) were seeded at 20000 cells/cm2 and incubated with complete medium supplemented with 1 μM dexamethasone, 0.45 mM isobutyl methylxanthine (IBMX), and 60 μM indomethacin
Heatmap classification showed a clustering of healthy donors (HDs) ASCs except for one donor
Summary
Multiple myeloma (MM) is a B cell neoplasia that accounts for approximately 1% of all cancers and 10% of hematologic neoplasias, with median age at diagnosis of about 70 years [1, 2]. Osteolytic bone disease develops in more than 80% of MM patients [3] and often leads to severe bone pain and pathologic fractures [4, 5] These irreversible symptoms have a huge impact on morbi-mortality in MM [6], resulting from excessive osteoclastic bone resorption and inhibited osteoblastic bone formation. More than 10 years ago, we hypothesized that autologous MSCs could be used in autologous stem cell transplantation for MM treatment because of their ability to differentiate to osteoblasts and support hematopoiesis [11]. Stem Cells International growth and differentiation factor 15 (GDF15), which is responsible for chemoprotection [8] Their ability to differentiate in osteoblasts is severely impaired, even without any contact with MM cells [16], one explanation being their abnormally high secretion of the Wnt inhibitor Dickkopf 1 (DKK1). This work presents a transcriptomic, phenotypic, and functional comparison of ASCs and MSCs from the same MM patients or healthy donors (HDs) to determine whether ASCs are suitable for treating bone disease in MM
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