Acute Leukemia Induces Senescence and Impaired Osteogenic Differentiation in Mesenchymal Stem Cells Endowing Leukemic Cells with Functional Advantages
Mesenchymal stem cells (MSC) constitute an important cell population of the bone marrow hematopoietic niche that supports normally hematopoietic stem cells (HSC) but eventually also leukemic cells. The alterations that occur in the MSC under leukemic stress are not well known. To deepen on this topi...
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Wiley
2019-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2019/3864948 |
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| author | Ximena Bonilla Natalia-Del Pilar Vanegas Jean Paul Vernot |
| author_facet | Ximena Bonilla Natalia-Del Pilar Vanegas Jean Paul Vernot |
| author_sort | Ximena Bonilla |
| collection | DOAJ |
| description | Mesenchymal stem cells (MSC) constitute an important cell population of the bone marrow hematopoietic niche that supports normally hematopoietic stem cells (HSC) but eventually also leukemic cells. The alterations that occur in the MSC under leukemic stress are not well known. To deepen on this topic, we have used an in vitro model of the leukemic niche (LN) by coculturing MSC with an acute lymphocytic leukemia cell line (REH) and proceeded to evaluate MSC characteristics and functions. We found that leukemic cells induced in MSC a significant increase both in senescence-associated β-galactosidase activity and in p53 gene expression. MSC in the LN also showed a persistent production of cytoplasmic reactive oxygen species (ROS) and a G2/M phase arrest of the cell cycle. Another acute leukemic cell line (SUP-B15) produced almost the same effects on MSC. REH cells adhere strongly to MSC possibly as a result of an increased expression of the adhesion molecules VCAM-1, ICAM-1, and CD49e in MSC and of CD49d in REH cells. Although mesensphere formation was normal or even increased, multipotent differentiation capacity was impaired in MSC from the LN. A REH-conditioned medium was only partially (about 50%) capable of inducing the same changes in MSC, suggesting that cell-to-cell contact is more efficient in inducing these changes. Despite these important effects on MSC in the LN, REH cells increased their cell adhesion, proliferation rate, and directed-migration capacity. In conclusion, in this in vitro LN model, leukemic cells affect importantly the MSC, inducing a senescence process that seems to favour leukemic cell growth. |
| format | Article |
| id | doaj-art-b91d961abdef4c2aa6ff71bd7b1f2e6b |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
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| series | Stem Cells International |
| spelling | doaj-art-b91d961abdef4c2aa6ff71bd7b1f2e6b2025-02-03T01:02:21ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/38649483864948Acute Leukemia Induces Senescence and Impaired Osteogenic Differentiation in Mesenchymal Stem Cells Endowing Leukemic Cells with Functional AdvantagesXimena Bonilla0Natalia-Del Pilar Vanegas1Jean Paul Vernot2Cellular and Molecular Physiology, Faculty of Medicine, Universidad Nacional de Colombia, Bogotá D.C. 111321, ColombiaCellular and Molecular Physiology, Faculty of Medicine, Universidad Nacional de Colombia, Bogotá D.C. 111321, ColombiaCellular and Molecular Physiology, Faculty of Medicine, Universidad Nacional de Colombia, Bogotá D.C. 111321, ColombiaMesenchymal stem cells (MSC) constitute an important cell population of the bone marrow hematopoietic niche that supports normally hematopoietic stem cells (HSC) but eventually also leukemic cells. The alterations that occur in the MSC under leukemic stress are not well known. To deepen on this topic, we have used an in vitro model of the leukemic niche (LN) by coculturing MSC with an acute lymphocytic leukemia cell line (REH) and proceeded to evaluate MSC characteristics and functions. We found that leukemic cells induced in MSC a significant increase both in senescence-associated β-galactosidase activity and in p53 gene expression. MSC in the LN also showed a persistent production of cytoplasmic reactive oxygen species (ROS) and a G2/M phase arrest of the cell cycle. Another acute leukemic cell line (SUP-B15) produced almost the same effects on MSC. REH cells adhere strongly to MSC possibly as a result of an increased expression of the adhesion molecules VCAM-1, ICAM-1, and CD49e in MSC and of CD49d in REH cells. Although mesensphere formation was normal or even increased, multipotent differentiation capacity was impaired in MSC from the LN. A REH-conditioned medium was only partially (about 50%) capable of inducing the same changes in MSC, suggesting that cell-to-cell contact is more efficient in inducing these changes. Despite these important effects on MSC in the LN, REH cells increased their cell adhesion, proliferation rate, and directed-migration capacity. In conclusion, in this in vitro LN model, leukemic cells affect importantly the MSC, inducing a senescence process that seems to favour leukemic cell growth.http://dx.doi.org/10.1155/2019/3864948 |
| spellingShingle | Ximena Bonilla Natalia-Del Pilar Vanegas Jean Paul Vernot Acute Leukemia Induces Senescence and Impaired Osteogenic Differentiation in Mesenchymal Stem Cells Endowing Leukemic Cells with Functional Advantages Stem Cells International |
| title | Acute Leukemia Induces Senescence and Impaired Osteogenic Differentiation in Mesenchymal Stem Cells Endowing Leukemic Cells with Functional Advantages |
| title_full | Acute Leukemia Induces Senescence and Impaired Osteogenic Differentiation in Mesenchymal Stem Cells Endowing Leukemic Cells with Functional Advantages |
| title_fullStr | Acute Leukemia Induces Senescence and Impaired Osteogenic Differentiation in Mesenchymal Stem Cells Endowing Leukemic Cells with Functional Advantages |
| title_full_unstemmed | Acute Leukemia Induces Senescence and Impaired Osteogenic Differentiation in Mesenchymal Stem Cells Endowing Leukemic Cells with Functional Advantages |
| title_short | Acute Leukemia Induces Senescence and Impaired Osteogenic Differentiation in Mesenchymal Stem Cells Endowing Leukemic Cells with Functional Advantages |
| title_sort | acute leukemia induces senescence and impaired osteogenic differentiation in mesenchymal stem cells endowing leukemic cells with functional advantages |
| url | http://dx.doi.org/10.1155/2019/3864948 |
| work_keys_str_mv | AT ximenabonilla acuteleukemiainducessenescenceandimpairedosteogenicdifferentiationinmesenchymalstemcellsendowingleukemiccellswithfunctionaladvantages AT nataliadelpilarvanegas acuteleukemiainducessenescenceandimpairedosteogenicdifferentiationinmesenchymalstemcellsendowingleukemiccellswithfunctionaladvantages AT jeanpaulvernot acuteleukemiainducessenescenceandimpairedosteogenicdifferentiationinmesenchymalstemcellsendowingleukemiccellswithfunctionaladvantages |