Stromal regulation of hemopoietic stem cells in long-term human bone marrow tissue cultures under the effect of parathyroid hormone

Petrova, Nadya; Svinareva, D. A.; Nifontova, I. N.; Momotyuk, K. S.; Vg, Savchenko; Ni, Drize

doi:10.1007/s10517-006-0408-5

Cited by 10 publications

(6 citation statements)

References 12 publications

(9 reference statements)

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“…PTH is known to activate osteoblasts in the niches where its presence improves the maintenance of hematopoiesis and adhesion of HSC to the stromal cells. 45 Accordingly, it was hypothesized that PTH may affect gene expression in LTBMC from AA patients or donors after treatment with AA serum. Our results show that the addition of PTH to these cultures normalized the pathological alterations.…”

Section: Discussionmentioning

confidence: 99%

Alterations in Hematopoietic Microenvironment in Patients with Aplastic Anemia

Shipounova

Petrova

Svinareva

et al. 2009

Clinical Translational Sci

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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: Discussionmentioning

confidence: 99%

Alterations in Hematopoietic Microenvironment in Patients with Aplastic Anemia

Shipounova

Petrova

Svinareva

et al. 2009

Clinical Translational Sci

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“…PTH is an approved polypeptide for the treatment of osteoporosis because it stimulates bone formation that results in increased bone mineral density with additional known effects on hematopoiesis. 23 Indeed, PTH can directly stimulate the proliferation and survival of HSPC, but it also partially exerts its effects through the OB 24 by increasing the production of Jagged 1 in OB, which in turn activates Notch receptors on nearby HSPC. Moreover, PTH has also been shown to act through the insulin-like growth factor pathway, which is specifically upregulated in OB, but not MSPCs in response to PTH.…”

Section: Impact Of Intrinsic and Extrinsic Factors On The Osteo-hematmentioning

confidence: 99%

Myelodysplasia is in the niche: novel concepts and emerging therapies

et al. 2014

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Myelodysplastic syndromes (MDSs) represent clonal disorders mainly of the elderly that are characterized by ineffective hematopoiesis and an increased risk of transformation into acute myeloid leukemia. The pathogenesis of MDS is thought to evolve from accumulation and selection of specific genetic or epigenetic events. Emerging evidence indicates that MDS is not solely a hematopoietic disease but rather affects the entire bone marrow microenvironment, including bone metabolism. Many of these cells, in particular mesenchymal stem and progenitor cells (MSPCs) and osteoblasts, express a number of adhesion molecules and secreted factors that regulate blood regeneration throughout life by contributing to hematopoietic stem and progenitor cell (HSPC) maintenance, self-renewal and differentiation. Several endocrine factors, such as erythropoietin, parathyroid hormone and estrogens, as well as deranged iron metabolism modulate these processes. Thus, interactions between MSPC and HSPC contribute to the pathogenesis of MDS and associated pathologies. A detailed understanding of these mechanisms may help to define novel targets for diagnosis and possibly therapy. In this review, we will discuss the scientific rationale of ‘osteohematology' as an emerging research field in MDS and outline clinical implications.

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“…At the same time, there is evidence of qualitative differences in hematopoiesis that is supported by stroma derived from different ontological environments. 17,18 In an hUCBDSC nude mouse transplantation study, we reported that by providing a cord blood-associated environment, we achieved higher concentrations and faster recovery of circulating platelets in the PB, suggesting that transplantation of hUCBDSCs qualitatively promotes megakaryocytopoiesis.…”

Section: Resultsmentioning

confidence: 93%