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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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Published in:PloS one 2013-11, Vol.8 (11), p.e76989
Main Authors: Conforti, Antonella, Biagini, Simone, Del Bufalo, Francesca, Sirleto, Pietro, Angioni, Adriano, Starc, Nadia, Li Pira, Giuseppina, Moretta, Francesca, Proia, Alessandra, Contoli, Benedetta, Genovese, Silvia, Ciardi, Claudia, Avanzini, Maria Antonietta, Rosti, Vittorio, Lo-Coco, Francesco, Locatelli, Franco, Bernardo, Maria Ester
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cited_by cdi_FETCH-LOGICAL-c758t-89ef69d2a98acfecc8d5976b39e99c880a660a0cb9910fc3e866021a66475fbc3
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creator Conforti, Antonella
Biagini, Simone
Del Bufalo, Francesca
Sirleto, Pietro
Angioni, Adriano
Starc, Nadia
Li Pira, Giuseppina
Moretta, Francesca
Proia, Alessandra
Contoli, Benedetta
Genovese, Silvia
Ciardi, Claudia
Avanzini, Maria Antonietta
Rosti, Vittorio
Lo-Coco, Francesco
Locatelli, Franco
Bernardo, Maria Ester
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
doi_str_mv 10.1371/journal.pone.0076989
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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&lt;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. 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Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Conforti, Antonella</au><au>Biagini, Simone</au><au>Del Bufalo, Francesca</au><au>Sirleto, Pietro</au><au>Angioni, Adriano</au><au>Starc, Nadia</au><au>Li Pira, Giuseppina</au><au>Moretta, Francesca</au><au>Proia, Alessandra</au><au>Contoli, Benedetta</au><au>Genovese, Silvia</au><au>Ciardi, Claudia</au><au>Avanzini, Maria Antonietta</au><au>Rosti, Vittorio</au><au>Lo-Coco, Francesco</au><au>Locatelli, Franco</au><au>Bernardo, Maria Ester</au><au>Menendez, Pablo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Biological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-11-07</date><risdate>2013</risdate><volume>8</volume><issue>11</issue><spage>e76989</spage><pages>e76989-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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&lt;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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24244271</pmid><doi>10.1371/journal.pone.0076989</doi><tpages>e76989</tpages><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
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issn 1932-6203
1932-6203
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subjects Abnormalities
Acute lymphoblastic leukemia
Acute lymphocytic leukemia
Adolescent
Analysis
Anemia
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Blood diseases
Bone marrow
Bone Marrow Cells - metabolism
Bone Marrow Cells - pathology
Cancer
Cell culture
Cell Differentiation - drug effects
Cell proliferation
Cells, Cultured
Chemotherapy
Child
Child health
Child, Preschool
Children & youth
Chromosomes
Cytogenetics
Diagnosis
Differentiation
Disease
Genetic abnormalities
Genetic aspects
Genetics
Hematology
Hematopoiesis
Hematopoiesis - drug effects
Hospitals
Humans
Immunomodulation
Infant
Laboratories
Leukemia
Lymphatic leukemia
Lymphocytes T
Male
Medical research
Mesenchymal stem cells
Mesenchymal Stromal Cells - metabolism
Mesenchymal Stromal Cells - pathology
Mesenchyme
Morphology
Oncology
Patients
Pediatrics
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism
Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology
Stem cells
Stromal cells
T cells
Time Factors
Translocation
title Biological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia
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