The ability of multipotent mesenchymal stromal cells from the bone marrow of patients with leukemia to maintain normal hematopoietic progenitor cells

Sorokina, Tamara; Shipounova, Irina N.; Bigildeev, Alexey; Petinati, Nataliya; Ni, Drize; Turkina, Anna; Chelysheva, Ekaterina; Shukhov, Oleg; Кузьмина, Л А; Паровичникова, Е Н; Vg, Savchenko

doi:10.1111/ejh.12713

Cited by 9 publications

(6 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Genes associated with quiescence and survival of stem/progenitor cells were increased such as ANGP51, SPP1, and SDF-1α [7]. Others have shown that AML-MSCs vs. ND-MSCs had decreased ability to support normal cobblestone area forming cells [56]. Other groups found no difference between AML-MSCs and ND-MSCs to support normal hematopoiesis in vitro [57].…”

Section: Discussionmentioning

confidence: 98%

Bone marrow mesenchymal stromal cells from acute myelogenous leukemia patients demonstrate adipogenic differentiation propensity with implications for leukemia cell support

et al. 2019

View full text Add to dashboard Cite

Bone marrow mesenchymal stromal cells (MSCs) constitute one of the important components of the hematopoietic microenvironmental niche. In vivo studies have shown that depletion of marrow MSCs resulted in reduction of hematopoietic stem cell content, and there is in vitro evidence that marrow MSCs are able to support leukemia progenitor cell proliferation and survival and provide resistance to cytotoxic therapies. How MSCs from leukemia marrow differ from normal counterparts and how they are influenced by the presence of leukemia stem and progenitor cells are still incompletely understood. In this work, we compared normal donor (ND) and acute myelogenous leukemia (AML) derived MSCs and found that AML-MSCs had increased adipogenic potential with improved ability to support survival of leukemia progenitor cells. To identify underlying changes, RNA-Seq analysis was performed. Gene ontology and pathway analysis revealed adipogenesis to be among the set of altered biological pathways dysregulated in AML-MSCs as compared with ND-MSCs. Expression of both SOX9 and EGR2 was decreased in AML-MSCs as compared with ND-MSCs. Increasing expression of SOX9 decreased adipogenic potential of AML-MSCs and decreased their ability to support AML progenitor cells. These findings suggest that AML-MSCs possess adipogenic potential which may enhance support of leukemia progenitor cells.

show abstract

Section: Discussionmentioning

confidence: 98%

Bone marrow mesenchymal stromal cells from acute myelogenous leukemia patients demonstrate adipogenic differentiation propensity with implications for leukemia cell support

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Their putative role in oncogenesis and leukemogenesis has not been fully clarified and the results from the studies already published are contradictory. In vitro studies have shown that MSCs from newly diagnosed adult patients with leukemia (acute myeloid leukemia and acute lymphoblastic leukemia) are less efficient for supporting normal hematopoietic progenitor cell survival and this functional capacity is partially restored after chemotherapy [ 5 ]. Their implication in childhood ALL has only recently being addressed, revealing that ALL-MSCs display reduced proliferative capacity and ability to support long-term hematopoiesis in vitro while those isolated at diagnosis did not differ from those obtained during treatment [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Biological Features of Bone Marrow Mesenchymal Stromal Cells in Childhood Acute Lymphoblastic Leukemia

Genitsari

Stiakaki

Perdikogianni

et al. 2018

Tjh

View full text Add to dashboard Cite

Objective:Mesenchymal stromal cells (MSCs) have a supportive role in hematopoiesis and as components of the bone marrow (BM) microenvironment may present alterations during acute lymphoblastic leukemia (ALL) and be affected by chemotherapeutic agents. We examined the biological and functional characteristics of MSCs in ALL diagnosis and treatment and their effect on MSC qualitative properties.Materials and Methods:Immunophenotypic characterization, evaluation of clonogenicity, and proliferative capacity were measured. Apoptotic features, cell-cycle analysis, and stromal cell-derived factor 1α and angiopoietin-1 levels in MSC supernatant at diagnosis and in different phases of treatment were assessed. Chemotherapy was administered according to the Berlin-Frankfurt-Munster-2000 protocol. BM samples from children with solid tumors without BM involvement were used as the control group.Results:The morphology, the immunophenotypic profile, and the apoptotic characteristics of the MSCs were not affected by leukemia. The secretion of factors involved in the trafficking of hematopoietic cells in the BM seems to be upregulated at diagnosis in comparison to the treatment phases. MSCs are influenced by the disease in terms of their functional characteristics such as clonogenicity and proliferation rate. These effects cease as soon as treatment is initiated. Chemotherapy does not seem to exert any effect on any of the MSC features examined.Conclusion:MSCs from children with ALL are affected by their interaction with the leukemic environment, but this phenomenon ceases upon treatment initiation, while no effect is observed by chemotherapy itself.

show abstract

“…In a malignant context, and more particularly in acute myeloid leukemia (AML), the most recent studies report functional abnormalities of human MSCs, which have a significant impact on the aggressiveness of the disease. Among these anomalies, growth deficiency, altered osteogenic differentiation ability and reduced capacity to support hematopoietic cells (26)(27)(28)(29)(30)(31) have been described, as well as modifications of the secretome (28,32), which induce in vivo shaping of the stromal niche by leukemic cells (33). Moreover, single cell analyses of murine BM stromal cells recently revealed that leukemia remodels the BM stroma to the disadvantage of normal hematopoietic cells.…”

Section: Heterogeneity Of Cafs/mscsmentioning

confidence: 99%

Deciphering Tumor Niches: Lessons From Solid and Hematological Malignancies

Mancini¹,

Balabanian²,

Corre³

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

Knowledge about the hematopoietic niche has evolved considerably in recent years, in particular through in vitro analyzes, mouse models and the use of xenografts. Its complexity in the human bone marrow, in particular in a context of hematological malignancy, is more difficult to decipher by these strategies and could benefit from the knowledge acquired on the niches of solid tumors. Indeed, some common features can be suspected, since the bone marrow is a frequent site of solid tumor metastases. Recent research on solid tumors has provided very interesting information on the interactions between tumoral cells and their microenvironment, composed notably of mesenchymal, endothelial and immune cells. This review thus focuses on recent discoveries on tumor niches that could help in understanding hematopoietic niches, with special attention to 4 particular points: i) the heterogeneity of carcinoma/cancer-associated fibroblasts (CAFs) and mesenchymal stem/stromal cells (MSCs), ii) niche cytokines and chemokines, iii) the energy/oxidative metabolism and communication, especially mitochondrial transfer, and iv) the vascular niche through angiogenesis and endothelial plasticity. This review highlights actors and/or pathways of the microenvironment broadly involved in cancer processes. This opens avenues for innovative therapeutic opportunities targeting not only cancer stem cells but also their regulatory tumor niche(s), in order to improve current antitumor therapies.

show abstract

The ability of multipotent mesenchymal stromal cells from the bone marrow of patients with leukemia to maintain normal hematopoietic progenitor cells

Abstract: The ability of patients' MSCs to maintain normal hematopoietic progenitor cells was shown to change in comparison with MSCs from healthy donors and depended on nosology. During treatment, the functional capacity of patients' MSCs had been partially restored.

Cited by 9 publications

References 46 publications

Bone marrow mesenchymal stromal cells from acute myelogenous leukemia patients demonstrate adipogenic differentiation propensity with implications for leukemia cell support

Bone marrow mesenchymal stromal cells from acute myelogenous leukemia patients demonstrate adipogenic differentiation propensity with implications for leukemia cell support

Biological Features of Bone Marrow Mesenchymal Stromal Cells in Childhood Acute Lymphoblastic Leukemia

Deciphering Tumor Niches: Lessons From Solid and Hematological Malignancies

Contact Info

Product

Resources

About