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Bone Marrow Multipotent Mesenchymal Stromal Cells from Patients with Aplastic Anemia Retain Their Ability to Support Hematopoietic Precursors despite Pronounced Changes in Gene Expression

  • Translated from Kletochnye Tekhnologii v Biologii i Meditsine (Cell Technologies in Biology and Medicine)
  • Published:
Bulletin of Experimental Biology and Medicine Aims and scope

The properties of bone marrow-derived multipotent mesenchymal stromal cells (MSC) of patients with aplastic anemia at the onset of the disease are studied insufficiently. The aim of this work was to test the ability of MSC from patients with aplastic anemia to maintain hematopoietic precursors and to analyze the expression of genes associated with hematopoiesis and immune response. The ability of MSC to maintain hematopoietic precursors was determined by counting cobblestone area-forming cells; gene expression was analyzed by quantitative PCR. It was shown that MSC of patients with aplastic anemia preserve their ability to maintain hematopoietic precursors. Pronounced changes in the expression of the VEGFA and ANGPT1 genes were found. MSC from aplastic anemia patients with PNH clone significantly differ from those from aplastic anemia patients without PNH clone in terms of the expression of the SDF1, IL1R, and VEGFA genes. Changes in gene expression can be associated with the pathogenesis of the disease.

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References

  1. Mihailova EA, Fidarova ZT, Troitskaya VV, Klyasova GA, Kulagin AD, Voronova EV, Dvirnyk VN, Galtseva IV, Kovrigina AM, Obukhova TN, Gapanova TV, Parovichnikova EN, Savchenko VG. Clinical recommendations for the diagnosis and treatment of aplastic anemia (2019 edition). Gematol. Transfusiol. 2020;65(2):208-226. doi: https://doi.org/10.35754/0234-5730-2020-65-2-208-226

  2. Sorokina TV, Shipunova IN, Bigildeev AE, Drize NI, Kuzmina LA, Parovichnikova EN, Savchenko VG. Modification of gene expression in mesenchymal stromal cells of the acute myeloid leukemia patients during chemotherapy. Gematol. Transfusiol. 2016;61(3):126-133. doi: https://doi.org/10.18821/0234-5730/2016-61-3-126-133

    Article  Google Scholar 

  3. Fidarova ZT, Abramova AV, Luchkin AV. Clone of paroxysmal nocturnal haemoglobinuria and other predictors of the response to immunosuppressive therapy in patients with idiopathic aplastic anaemia. Gematol. Transfusiol. 2019;64(3):342-352. doi: https://doi.org/10.35754/0234-5730-2019-64-3-342-352

    Article  Google Scholar 

  4. Agarwal P, Isringhausen S, Li H, Paterson AJ, He J, Gomariz Á, Nagasawa T, Nombela-Arrieta C, Bhatia R. Mesenchymal niche-specific expression of Cxcl12 controls quiescence of treatment-resistant leukemia stem cells. Cell Stem Cell. 2019;24(5):769-784.e6. doi: https://doi.org/10.1016/j.stem.2019.02.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bigildeev AE, Zhironkina OA, Lubkova ON, Drize NJ. Interleukin- 1 beta is an irradiation-induced stromal growth factor. Cytokine. 2013;64(1):131-137. doi: https://doi.org/10.1016/j.cyto.2013.07.003

    Article  CAS  PubMed  Google Scholar 

  6. Blank U, Karlsson S. TGF-β signaling in the control of hematopoietic stem cells. Blood. 2015;125(23):3542-3550. doi: https://doi.org/10.1182/blood-2014-12-618090

    Article  CAS  PubMed  Google Scholar 

  7. Kuzmina LA, Petinati NA, Parovichnikova EN, Lubimova LS, Gribanova EO, Gaponova TV, Shipounova IN, Zhironkina OA, Bigildeev AE, Svinareva DA, Drize NJ, Savchenko VG. Multipotent mesenchymal stromal cells for the prophylaxis of acute graft-versus-host disease — a Phase II Study. Stem Cells Int. 2012;2012:968213. doi: https://doi.org/10.1155/2012/968213

    Article  CAS  PubMed  Google Scholar 

  8. Luzzatto L, Risitano AM. Advances in understanding the pathogenesis of acquired aplastic anaemia. Br. J. Haematol. 2018;182(6):758-776. doi: https://doi.org/10.1111/bjh.15443

    Article  PubMed  Google Scholar 

  9. Maciejewski JP, Selleri C, Sato T, Anderson S, Young NS. A severe and consistent deficit in marrow and circulating primitive hematopoietic cells (long-term culture-initiating cells) in acquired aplastic anemia. Blood. 1996;88(6):1983-1991.

    Article  CAS  Google Scholar 

  10. Manier S, Sacco A, Leleu X, Ghobrial IM, Roccaro AM. Bone marrow microenvironment in multiple myeloma progression. J. Biomed. Biotechnol. 2012;2012:157496. doi: https://doi.org/10.1155/2012/157496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Medyouf H. The microenvironment in human myeloid malignancies: emerging concepts and therapeutic implications. Blood. 2017;129(12):1617-1626. doi: https://doi.org/10.1182/blood-2016-11-696070

    Article  CAS  PubMed  Google Scholar 

  12. Ploemacher RE, van der Sluijs JP, van Beurden CA, Baert MR, Chan PL. Use of limiting-dilution type long-term marrow cultures in frequency analysis of marrow-repopulating and spleen colony-forming hematopoietic stem cells in the mouse. Blood. 1991;78(10):2527-2533.

    Article  CAS  Google Scholar 

  13. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat. Protoc. 2008;3(6):1101-1108. doi: https://doi.org/10.1038/nprot.2008.73

    Article  CAS  PubMed  Google Scholar 

  14. Shipounova IN, Petrova TV, Svinareva DA, Momotuk KS, Mikhailova EA, Drize NI. Alterations in hematopoietic microenvironment in patients with aplastic anemia. Clin. Transl. Sci. 2009;2(1):67-74. doi: https://doi.org/10.1111/j.1752-8062.2008.00074.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Somasundaram V, Tevatia M.S, Purohit A, Ahuja A, Mahapatra M, Tyagi S, Pati H, Saxena R. Evaluation of bone marrow microvessel density in patients with aplastic anemia. Indian J. Hematol. Blood Transfus. 2017;33(2):169-174. doi: https://doi.org/10.1007/s12288-016-0707-6

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Correspondence to A. I. Dorofeeva.

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Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 4, pp. 233-237, December, 2021

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Dorofeeva, A.I., Shipunova, I.N., Drize, N.I. et al. Bone Marrow Multipotent Mesenchymal Stromal Cells from Patients with Aplastic Anemia Retain Their Ability to Support Hematopoietic Precursors despite Pronounced Changes in Gene Expression. Bull Exp Biol Med 172, 637–641 (2022). https://doi.org/10.1007/s10517-022-05453-y

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  • DOI: https://doi.org/10.1007/s10517-022-05453-y

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