Biological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia.
Alterations in hematopoietic microenvironment of acute lymphoblastic leukemia patients have been claimed to occur, but little is known about the components of marrow stroma in these patients. In this study, we characterized mesenchymal stromal cells (MSCs) isolated from bone marrow (BM) of 45 pediat...
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2013
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oai:doaj.org-article:ca9448cc504347e6a3a6100ba6e669582021-11-18T08:47:58ZBiological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia.1932-620310.1371/journal.pone.0076989https://doaj.org/article/ca9448cc504347e6a3a6100ba6e669582013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24244271/?tool=EBIhttps://doaj.org/toc/1932-6203Alterations in hematopoietic microenvironment of acute lymphoblastic leukemia patients have been claimed to occur, but little is known about the components of marrow stroma in these patients. In this study, we characterized mesenchymal stromal cells (MSCs) isolated from bone marrow (BM) of 45 pediatric patients with acute lymphoblastic leukemia (ALL-MSCs) at diagnosis (day+0) and during chemotherapy treatment (days: +15; +33; +78), the time points being chosen according to the schedule of BM aspirates required by the AIEOP-BFM ALL 2009 treatment protocol. Morphology, proliferative capacity, immunophenotype, differentiation potential, immunomodulatory properties and ability to support long-term hematopoiesis of ALL-MSCs were analysed and compared with those from 41 healthy donors (HD-MSCs). ALL-MSCs were also genetically characterized through array-CGH, conventional karyotyping and FISH analysis. Moreover, we compared ALL-MSCs generated at day+0 with those isolated during chemotherapy. Morphology, immunophenotype, differentiation potential and in vitro life-span did not differ between ALL-MSCs and HD-MSCs. ALL-MSCs showed significantly lower proliferative capacity (p<0.001) and ability to support in vitro hematopoiesis (p = 0.04) as compared with HD-MSCs, while they had similar capacity to inhibit in vitro mitogen-induced T-cell proliferation (p = N.S.). ALL-MSCs showed neither the typical translocations carried by the leukemic clone (when present), nor other genetic abnormalities acquired during ex vivo culture. Our findings indicate that ALL-MSCs display reduced ability to proliferate and to support long-term hematopoiesis in vitro. ALL-MSCs isolated at diagnosis do not differ from those obtained during treatment.Antonella ConfortiSimone BiaginiFrancesca Del BufaloPietro SirletoAdriano AngioniNadia StarcGiuseppina Li PiraFrancesca MorettaAlessandra ProiaBenedetta ContoliSilvia GenoveseClaudia CiardiMaria Antonietta AvanziniVittorio RostiFrancesco Lo-CocoFranco LocatelliMaria Ester BernardoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e76989 (2013) |
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Medicine R Science Q Antonella Conforti Simone Biagini Francesca Del Bufalo Pietro Sirleto Adriano Angioni Nadia Starc Giuseppina Li Pira Francesca Moretta Alessandra Proia Benedetta Contoli Silvia Genovese Claudia Ciardi Maria Antonietta Avanzini Vittorio Rosti Francesco Lo-Coco Franco Locatelli Maria Ester Bernardo Biological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia. |
| description |
Alterations in hematopoietic microenvironment of acute lymphoblastic leukemia patients have been claimed to occur, but little is known about the components of marrow stroma in these patients. In this study, we characterized mesenchymal stromal cells (MSCs) isolated from bone marrow (BM) of 45 pediatric patients with acute lymphoblastic leukemia (ALL-MSCs) at diagnosis (day+0) and during chemotherapy treatment (days: +15; +33; +78), the time points being chosen according to the schedule of BM aspirates required by the AIEOP-BFM ALL 2009 treatment protocol. Morphology, proliferative capacity, immunophenotype, differentiation potential, immunomodulatory properties and ability to support long-term hematopoiesis of ALL-MSCs were analysed and compared with those from 41 healthy donors (HD-MSCs). ALL-MSCs were also genetically characterized through array-CGH, conventional karyotyping and FISH analysis. Moreover, we compared ALL-MSCs generated at day+0 with those isolated during chemotherapy. Morphology, immunophenotype, differentiation potential and in vitro life-span did not differ between ALL-MSCs and HD-MSCs. ALL-MSCs showed significantly lower proliferative capacity (p<0.001) and ability to support in vitro hematopoiesis (p = 0.04) as compared with HD-MSCs, while they had similar capacity to inhibit in vitro mitogen-induced T-cell proliferation (p = N.S.). ALL-MSCs showed neither the typical translocations carried by the leukemic clone (when present), nor other genetic abnormalities acquired during ex vivo culture. Our findings indicate that ALL-MSCs display reduced ability to proliferate and to support long-term hematopoiesis in vitro. ALL-MSCs isolated at diagnosis do not differ from those obtained during treatment. |
| format |
article |
| author |
Antonella Conforti Simone Biagini Francesca Del Bufalo Pietro Sirleto Adriano Angioni Nadia Starc Giuseppina Li Pira Francesca Moretta Alessandra Proia Benedetta Contoli Silvia Genovese Claudia Ciardi Maria Antonietta Avanzini Vittorio Rosti Francesco Lo-Coco Franco Locatelli Maria Ester Bernardo |
| author_facet |
Antonella Conforti Simone Biagini Francesca Del Bufalo Pietro Sirleto Adriano Angioni Nadia Starc Giuseppina Li Pira Francesca Moretta Alessandra Proia Benedetta Contoli Silvia Genovese Claudia Ciardi Maria Antonietta Avanzini Vittorio Rosti Francesco Lo-Coco Franco Locatelli Maria Ester Bernardo |
| author_sort |
Antonella Conforti |
| title |
Biological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia. |
| title_short |
Biological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia. |
| title_full |
Biological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia. |
| title_fullStr |
Biological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia. |
| title_full_unstemmed |
Biological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia. |
| title_sort |
biological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/ca9448cc504347e6a3a6100ba6e66958 |
| work_keys_str_mv |
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