Effect of the bone marrow mesenchymal stromal cells cytokine-producing activity on mobilization of hematopoietic stem cells

Author:

Poponina E. A.1ORCID,Pestrikova A. O.1ORCID,Nazarova E. L.1ORCID,Isaeva N. V.1ORCID,Fokina E. S.1ORCID,Endakova A. I.1,Minaeva N. V.1ORCID

Affiliation:

1. The Federal State-Financed Scientific Institution Kirov Research Institute of Hematology and Blood Transfusion under the Federal Medical Biological Agency (KRIHBT)

Abstract

Hematopoietic stem cell transplantation is used to treat hemoblastoses and some other diseases. Depending on the diagnosis, autologous cells of the patient or allogeneic cells obtained from a healthy related or unrelated donor are used. A sufficient count of harvested hematopoietic progenitor cells is necessary for successful transplantation. Currently, stimulation of their egress from the bone marrow into the peripheral blood by a granulocyte colony-stimulating factor, followed by collection by leukapheresis, is widely used for their preparation. Hematopoietic stem cells leave the bone marrow niche formed by the stromal microenvironment when their holding bonds are interrupted. Mesenchymal stromal cells regulate the release of hematopoietic precursors by producing various cytokines and other biologically active substances. Therefore, the study of the functional properties of bone marrow mesenchymal cells can help in solving the problem of “poor” mobilizations that occur in patients with multiple myeloma.The aim of the study was to estimate the effectiveness of mobilization of hematopoietic stem cells depending on the cytokine-producing ability of mesenchymal stromal cells in the bone marrow of donors and patients with multiple myeloma.The yields of hematopoietic progenitors were studied in 10 donors (median age 27 years) and 18 patients with multiple myeloma (median age 57 years). In donors, the release of hematopoietic stem cells into the peripheral blood was stimulated by subcutaneous administration of G-CSF at a dose of 10 μg/kg/day. Patients with multiple myeloma received vinorelbine at a dose of 35 mg/m2 of body surface, followed by administration of G-CSF (10 μg/kg/day subcutaneously). A culture of mesenchymal stromal cells was obtained from bone marrow taken prior to mobilization and the content of interleukins IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α and IFN-γ in supernatants was studied by enzyme-linked immunosorbent assay using kits of reagents produced by Vector-Best (Novosibirsk).Patients with multiple myeloma were characterized by high secretion of the pro-inflammatory cytokine IL-2 (4.70 pg/ml vs 3.55 pg/ml in healthy individuals, p=0.003) and low IFN-γ (0.41 pg/ml vs 2.14 pg/ml in healthy, p<0.001), but no relationship was found between these cytokines and the hematopoietic stem cells yield. The present study showed that in patients with ineffective harvesting of hematopoietic precursors, secretion of IL-8 by stromal cells was low (308.08 pg/ml vs 561.29 pg/ml in healthy individuals, p=0.04).The obtained results are consistent with the literature data on the important role of IL-8 in the mobilization of hematopoietic stem cells, which allows to consider IL-8 as an informative marker for predicting the insufficient yields of hematopoietic precursors.

Publisher

SPb RAACI

Reference8 articles.

1. Kostroma I.I., Zhernyakova A.A., Chubukina Zh.V., Zapreeva I.M., Tiranova S.A., Seltser A.V., Semenova N.Yu., Bessmeltsev S.S., Chechetkin A.V., Gritsaev S.V. Hematopoietic stem cell collection in multiple myeloma patients: influence of the lenalidomide-based therapy and mobilization regimen prior to auto-HSCT. Klinicheskaya onkogematologiya = Clinical Oncohematology, 2018, Vol. 11, no. 2, pp. 192-197. (In Russ.)]

2. Rugal V.I., Bessmeltsev S.S., Semenova N.Yu., Gritsaev S.V., Kostroma I.I., Enukashvili N.I., Chubar A.V., Ivolgin D.A. Characteristics of bone marrow microenvironment in multiple myeloma before and after treatment. Sibirskiy nauchnyy meditsinskiy zhurnal = Siberian Scientific Medical Journal, 2019, Vol. 39, no. 1, pp. 112-118. (In Russ.)

3. Fedyk O.V., Sarzhevskiy V.O., Melnichenko V.Ya., Dubinina Yu.N., Mochkin N.E., Smirnova E.G., Kolesnikova D.S., Bannikova A.E. Autologous transplantation in patients with lymphoproliferative diseases: does everyone manage to get a sufficient number of peripheral hematopoietic stem cells? Vestnik Natsionalnogo mediko-khirurgicheskogo Tsentra im. N.I. Pirogova. Onkogematologiya = Bulletin of Pirogov National Medical and Surgical Center, 2018, Vol. 13, no. 3, pp. 67-71. (In Russ.)

4. Bendall L.J., Bradstock K.F. G-CSF: From granulopoietic stimulant to bone marrow stem cell mobilizing agent. Cytokine Growth Factor Rev., 2014, Vol. 25, no. 4, pp. 355-367.

5. Carreras E., Dufour C., Mohty M., Kröger N., editors. The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies [Internet]. 7th ed. Cham (CH): Springer; 2019.

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3