Bone Marrow Stromal Cells in Myeloproliferative Disorders

Hirata, Jouji; Takahira, Hiroyuki; Kaneko, Shushi; Nishimura, Junji; Nawata, Hajime

doi:10.1159/000205275

Cited by 12 publications

(12 citation statements)

References 12 publications

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“…32 Taken together with our observation of impaired adipogenic differentiation of AA MSC including morphological abnormalities and decreased level of IGF-1 expression, the data hint that adipogenic differentiation is impaired at times that correlate with the worst phases of hematopoietic depression. Fat cells are necessary for the adequate maintenance of hematopoiesis, and their dysfunction in the worst phase of the disease points to the existence of secondary alterations in MSC of AA patients.…”

Section: Discussionsupporting

confidence: 61%

“…[26][27][28] The CFU-F concentration in the BM varies among patients with different hematologic diseases, [29][30][31] and it may also depend on the treatment or phase of the disease. 7,32,33 The characteristics of CFU-F could therefore potentially be used for monitoring the function of the stromal microenvironment over the course of the disease.…”

Section: Introductionmentioning

confidence: 99%

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Alterations in Hematopoietic Microenvironment in Patients with Aplastic Anemia

Shipounova¹,

Petrova²,

Svinareva³

et al. 2009

Clinical and Translational Science

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Mechanisms of hematopoietic failure in patients with aplastic anemia (AA) are obscure. We investigate alterations in the hematopoietic microenvironment in AA patients. We present the results of studying mesenchymal stromal cells (MSC), fibroblastic colony-forming units (CFU-F), and adherent cell layers (ACL) of long-term bone marrow cultures (LTBMC) from bone marrow (BM) samples of AA patients. MSC of AA patients proliferated longer than those of donors. In half of the patients' MSC cultures, adipogenesis was impaired. Osteogenic differentiation was not achieved in 36% of AA MSC. CFU-F formed enlarged colonies, and their concentration in the BM of AA patients was significantly increased. Our data suggest that the physiological activation of the stromal microenvironment is characteristic of AA. We detected a decrease in the expression of the angiopoetin-1 (ANG-1) and vascular cell adhesion molecule-1 (VCAM-1) genes, together with an increase in the expression of vascular endothelial growth factor (VEGF) in ACL of AA patients. This indicates abnormal regulatory patterns in both osteoblastic and vascular contexts. Addition of AA patients' serum to donors' LTBMC for 3 weeks induced similar gene expression alterations. The addition of parathyroid hormone (PTH) resulted in the expression levels of analyzed genes returning to normal, in both AA LTBMC and donor cultures treated with AA serum. The physiologic status of the BM stromal microenvironment (MSC, CFU-F, and ACL of LTBMC) of AA patients was altered.

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Section: Discussionsupporting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Alterations in Hematopoietic Microenvironment in Patients with Aplastic Anemia

Shipounova¹,

Petrova²,

Svinareva³

et al. 2009

Clinical and Translational Science

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“…3) [22]. This was not explained by changes in the production of any of the known stimulatory or inhibitory cytokines [22,101,173,214,215].…”

Section: Stromal Abnormalities In CMLmentioning

confidence: 99%

“…CML fibroblasts exhibited the same proliferative behavior and protein synthesizing capacity as normal fibroblasts [34]. In the majority of cases reported, the numbers of CFU-F were within the normal range [23,101,114,162,219]. The number of adipocyte colony-forming cells was often increased [101], a finding which is difficult to reconcile with the already mentioned reduction in fat cells in histological sections [130].…”

Section: Stromal Abnormalities In CMLmentioning

confidence: 99%

Stromal abnormalities in neoplastic bone marrow diseases

Dührsen

Hossfeld

1996

Annals of Hematology

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Bone marrow malignancies are clonal disorders resulting from neoplastic transformation of hematopoietic stem or progenitor cells. Similar to their normal counterparts, transformed blood-forming cells remain dependent on signals from the hematopoiesis-regulating stromal environment for survival and proliferation. There is increasing evidence that the microenvironment may also take a more active part in the disease process. A review of the literature on stromal abnormalities in the leukemias, the myelodysplastic syndromes, and multiple myeloma reveals three principal mechanisms by which stromal derangements can contribute to the evolution of a neoplastic disease. In the simplest case, neoplastic blood-forming cells induce reversible changes in stroma function or composition which result in improved growth conditions for the malignant cells ('malignancy-induced microenvironment'). In the second setting, functionally abnormal end cells derived from the malignant clone become an integral part of the stroma system, selectively stimulating the neoplastic cells and inhibiting normal blood cell formation ('malignant microenvironment'). In the third condition, the emergence of a neoplastic cell population is the consequence of a primary stroma lesion characterized by inability to control regular blood cell formation ('malignancy-inducing microenvironment'). The perception of different stroma-related disease mechanisms may eventually lead to the development of alternative therapeutic approaches.

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“…Nevertheless, such patients often later progress to myelofibrosis. Analysis of CFU-F in the bone marrow of the patients with chronic myeloid leukemia and polycythemia vera revealed that the growth characteristics of this precursor were unchanged [16, 17]. Summarizing the data, one could suggest a possible interconnection between the quality of hematopoiesis and the functional status of the stromal microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Sensitivity of Mesenchymal Stem Cells and Their Progeny to Medicines Used for the Treatment of Hematoproliferative Diseases

Nifontova¹,

Svinareva²,

Petrova³

et al. 2008

Acta Haematol

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Background/Aims: The influence of cytostatic medicines on mesenchymal stem cells (MSC) and their progeny, fibroblastic colony-forming units (CFU-F), was investigated. Methods: Mice were treated with busulfan, cyclophosphamide, cytarabine, methotrexate and bortezomib, as used in clinical practice. MSC and CFU-F were analyzed 3 days and 6 weeks after the treatment termination. To estimate MSC numbers, the ectopic foci formation method was used. Briefly, a donor bone marrow plug was transplanted under the renal capsule of a syngeneic animal, leading to ectopic foci formation. The systemic response of the hematopoietic microenvironment to these drugs was studied using the same method applied to recipients pretreated with the medicines. Results: CFU-F concentration was halved in the bone marrow of mice treated with busulfan, methotrexate and cyclophosphamide, and was not restored for the next 6 weeks. Proliferative potential and differentiation abilities of MSC were not affected by these medicines. The enlargement of foci size in mice treated with cytostatic agents was not conditioned by MSC, but by more mature stromal precursor cells. Conclusions: Cytostatic medicines affect stromal precursors in 2 ways: they decrease CFU-F concentration in the ‘steady-state’ bone marrow, while stimulating growth of the stromal microenvironment during its de novo formation. MSC are not sensitive to the cytostatic agents used.

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Bone Marrow Stromal Cells in Myeloproliferative Disorders

Cited by 12 publications

References 12 publications

Alterations in Hematopoietic Microenvironment in Patients with Aplastic Anemia

Alterations in Hematopoietic Microenvironment in Patients with Aplastic Anemia

Stromal abnormalities in neoplastic bone marrow diseases

Sensitivity of Mesenchymal Stem Cells and Their Progeny to Medicines Used for the Treatment of Hematoproliferative Diseases

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