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Functional comparison between healthy and multiple myeloma adipose stromal cells

ABSTRACT: Multiple myeloma (MM) is a not curable B-cell neoplasia characterised by the accumulation of tumor plasma cells within the bone marrow. As a consequence, 80% of patients develop bone osteolytic lesions that remain even after complete remission. We and others had demonstrated that bone marrow derived Mesenchymal Stromal Cells (MSC) are abnormal in MM and thus could not be used for an autologous treatment to repare bone damages. Adipose Stromal Cells (ASC) represent an interesting alternative to MSC for cellular therapy. Thus, in this paper we asked if they could be a good candidate in repairing MM bone lesions. For the first time, we present a transcriptomic, phenotypic and functional comparison between ASC from MM patients and healthy donors (HD) relying on their autologous MSC counterpart. In contrast to MM MSC, MM ASC do not exhibit major abnormalities. However, the changes observed in MM ASC and the supportive property of ASC on MM cells question their putative and safety uses at autologous or allogenic level.

ORGANISM(S): Homo sapiens

PROVIDER: GSE133346 | GEO | 2019/06/27

REPOSITORIES: GEO

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Project description:The unique properties of the bone marrow allow for migration and proliferation of multipl myeloma (MM) cells, while also providing the perfect environment for development of quiescent, drug-resistant MM cell clones. Bone marrow adipocytes (BMAds), which have recently been identified as important contributors to systemic adipokine levels, bone strength, hematopoiesis, and progression of metastatic and primary bone marrow cancers, such as MM. Recent studies in myeloma suggest that BMAds can be reprogrammed by tumor cells to contribute to myeloma-induced bone disease, and reciprocally, BMAds support MM cells in vitro. Importantly, most data investigating BMAds have been generated using adipocytes derived by differentiating bone marrow-derived mesenchymal stromal cells (MSCs) into adipocytes in vitro using adipogenic media, due to the extreme technical challenges associated with isolating and culturing primary adipocytes. However, if studies could be performed with primary adipocytes, they likely will recapitulate in vivo biology better than MSC-derived adipocyte, as the differentiation process is artificial and differs from in vivo differentiation, and progenitor cell(s) of the primary BMAd may not be the same as the MSCs precursors used for adipogenic differentiation in vitro. Therefore, we developed and refined three methods for culturing primary BMAds (pBMAds): 2D coverslips, 2D transwells, and 3D silk scaffolds, all of which can be cultured alone or with MM cells to investigate bidirectional tumor-host signaling. To develop an in vitro model with a tissue-like structure to mimic the bone marrow microenvironment, we developed the first 3D, tissue engineered model utilizing pBMAds derived from human bone marrow. We found that pBMAds, which are extremely fragile, can be isolated and stably cultured in 2D for 10 days and in 3D for short term (~2 weeks) or long term (1 month) in vitro. To investigate the relationship between pBMAds and myeloma, MM cells can be added to investigate physical relationships through confocal imaging and soluble signaling molecules via mass spectrometry. In sum, we developed three in vitro cell culture systems to study primary bone marrow adipocytes and myeloma cells, which could be adapted to investigate many diseases and biological processes involving the bone marrow, including other bone-homing tumor types.

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Functional comparison between healthy and multiple myeloma adipose stromal cells

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