Characterization of freshly isolated bone marrow mesenchymal stromal cells from healthy donors and patients with multiple myeloma: transcriptional modulation of the microenvironment

Alameda, Daniel; Sáez, Borja; Lara‐Astiaso, David; Sarvide, Sarai; Lasa, Marta; Alignani, Diego; Rodríguez, Idoia; Gárate, Sonia; Vilas, Amaia; Alfonso-Olmos, Matías; Espinosa, J.; Prósper, Felipe; Miguel, Jesús F. San; Maiso, Patricia

doi:10.3324/haematol.2019.235135

Cited by 19 publications

(31 citation statements)

References 23 publications

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“…MSCs might affect the etiological events at HSC and B progenitor levels, which contribute to the progression of MM in some patients [170,171]. The effects of MM treatment on MSCs are also largely unknown [76]. In the near future, the improvement in humanized mouse models with advances in gene transduction methods and construction of three-dimensional tissues with scaffold could yield valuable information.…”

Section: Discussionmentioning

confidence: 99%

“…In 2000s, genetic analyses with MM-MSCs demonstrated that transcriptomes, such as IL-6, DKK1 and growth differentiation factor (GDF)15, which regulate angiogenesis, osteogenic differentiation, and tumor growth, were distinctively expressed in MM-MSCs, as compared to ND-MSCs [73,74]. Another study using bioinformatics analyses showed that the genes associated with cell cycle, immune response, and bone metabolism were significantly regulated [75][76][77]. In vitro experiments with a co-culture system indicated that the supportive capacity of T-cell proliferation was impaired with high expression of IL-6 by MM-MSCs [78,79].…”

Section: Studies With Human Mscsmentioning

confidence: 99%

“…On the other hand, recent technical advances in flow cytometry have enabled the isolation of MSCs, which express several surface markers, such as CD271, CD146, SSEA4, CD49a, and PDGF receptors in human, without maintaining cell cultures. It has been reported that there are differences between freshly isolated and cultured MSCs in terms of expression of RNAs, cell surface molecules, and the reconstitution capacity in vivo [76,[112][113][114][115]. Although the experimental results mentioned above were acquired from studies with MSCs derived from patients, it is possible that MSCs isolation method might affect the results.…”

Section: Studies With Human Mscsmentioning

confidence: 99%

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Current Understanding of Myelomatous Mesenchymal Stromal Cells Extended through Advances in Experimental Methods

Ichii

Hosen

2020

Cancers

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Multiple myeloma is an incurable cancer formed by malignant plasma cells. For the proliferation and survival of myeloma cells, as well as the occurrence of the complications, numerous intra- and extra-cellular mechanisms are involved. The interaction of myeloma cells with the microenvironment is known to be one of the most critical mechanisms. A specific microenvironment could affect the progression and growth of tumor cells, as well as drug resistance. Among various microenvironment components, such as hematological and non-hematological cells, and soluble factors (cytokines, chemokines, and extracellular matrix (ECM) proteins), in this review, we focus on the role of mesenchymal cells. We aimed to summarize the experimental strategies used for conducting studies and current understanding of the biological roles in the pathogenesis of myeloma. Furthermore, we discuss the possible clinical applications targeting mesenchymal cells.

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Section: Discussionmentioning

confidence: 99%

Section: Studies With Human Mscsmentioning

confidence: 99%

Section: Studies With Human Mscsmentioning

confidence: 99%

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Current Understanding of Myelomatous Mesenchymal Stromal Cells Extended through Advances in Experimental Methods

Ichii

Hosen

2020

Cancers

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“…However, other studies comparing BM-MSCs harvested from young and old donors have shown both a maintenance [ 78 , 79 ] or a decrease in the osteogenic differentiation of oldest BM-MSCs [ 30 , 80 , 81 , 82 ]. In a recent study, authors analyzed the transcriptional profile of freshly isolated BM-MSCs from young and old donors and showed the upregulation of genes implicated in the peroxisome proliferator-activated receptor (PPAR) signaling in the oldest group, suggesting a reinforcement of pro-adipogenic microenvironment with aging [ 83 ].…”

Section: The Role Of Bm-mscs In Bm and Hematopoiesis Alterations Dmentioning

confidence: 99%

Aging of Bone Marrow Mesenchymal Stromal Cells: Hematopoiesis Disturbances and Potential Role in the Development of Hematologic Cancers

Massaro

Corrillon

Stamatopoulos

et al. 2020

Cancers

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Aging of bone marrow is a complex process that is involved in the development of many diseases, including hematologic cancers. The results obtained in this field of research, year after year, underline the important role of cross-talk between hematopoietic stem cells and their close environment. In bone marrow, mesenchymal stromal cells (MSCs) are a major player in cell-to-cell communication, presenting a wide range of functionalities, sometimes opposite, depending on the environmental conditions. Although these cells are actively studied for their therapeutic properties, their role in tumor progression remains unclear. One of the reasons for this is that the aging of MSCs has a direct impact on their behavior and on hematopoiesis. In addition, tumor progression is accompanied by dynamic remodeling of the bone marrow niche that may interfere with MSC functions. The present review presents the main features of MSC senescence in bone marrow and their implications in hematologic cancer progression.

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“…A reduced lymphocyte count is considered a poor prognostic factor in malignancy, suggesting an important role for immunosurveillance and clearance of lymphocytes [ 12 ]. The survival of MM cells depends on their interaction with the microenvironment [ 13 ]. A new prognostic evaluation system that incorporates immune-related biomarkers is urgently needed.…”

Section: Introductionmentioning

confidence: 99%

Peripheral Absolute Lymphocyte Count: An Economical and Clinical Available Immune-Related Prognostic Marker for Newly Diagnosed Multiple Myeloma

Liu

Wang

2020

Med Sci Monit

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Background To find economical and clinically available immune-related prognostic markers that could predict the overall survival (OS) of newly diagnosed multiple myeloma (NDMM) in the new drug era. Material/Methods Absolute lymphocyte count (ALC) and absolute monocyte count (AMC) were measured in routine blood samples from 102 patients with NDMM, and the lymphocyte-monocyte ratio (LMR) was derived. All the patients were receiving bortezomib-based chemotherapy as induction treatment. Log-rank testing was used for comparing the differences between groups. Univariate and multivariate tests were used to identify prognostic markers. Results The median ALC and LMR values at diagnosis were 1.43×10 9 /L and 3.7, respectively, and served as the cutoff point. As prognostic factors, ALC, LMR, and a new staging system combining ALC and the ISS staging system (L-ISS) were expected to have a significant impact on predicting OS. Furthermore, multivariate analysis showed that ALC ≥1.43×10 9 /L (hazard ratio [HR]: 0.223; 95% confidence interval [CI]: 0.071–0.705; P =0.011), LMR ≥3.7 (HR: 0.363; 95% CI: 0.139–0.947; P =0.038), and L-ISS late stage (HR: 1.619; 95% CI: 1.065–2.743; P =0.027) were independent predictors for OS. Conclusions ALC and LMR can serve as surrogate markers for patients’ antitumor immunity at the initial diagnosis of multiple myeloma. A new immune-related staging system, L-ISS, which combines ALC and the ISS staging system, can predict clinical outcomes in patients who are receiving bortezomib-based chemotherapy.

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Characterization of freshly isolated bone marrow mesenchymal stromal cells from healthy donors and patients with multiple myeloma: transcriptional modulation of the microenvironment

Cited by 19 publications

References 23 publications

Current Understanding of Myelomatous Mesenchymal Stromal Cells Extended through Advances in Experimental Methods

Current Understanding of Myelomatous Mesenchymal Stromal Cells Extended through Advances in Experimental Methods

Aging of Bone Marrow Mesenchymal Stromal Cells: Hematopoiesis Disturbances and Potential Role in the Development of Hematologic Cancers

Peripheral Absolute Lymphocyte Count: An Economical and Clinical Available Immune-Related Prognostic Marker for Newly Diagnosed Multiple Myeloma

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