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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 |
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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 |
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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<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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0076989</identifier><identifier>PMID: 24244271</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PloS one, 2013-11, Vol.8 (11), p.e76989</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Conforti et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Conforti et al 2013 Conforti et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-89ef69d2a98acfecc8d5976b39e99c880a660a0cb9910fc3e866021a66475fbc3</citedby><cites>FETCH-LOGICAL-c758t-89ef69d2a98acfecc8d5976b39e99c880a660a0cb9910fc3e866021a66475fbc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1449331977/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1449331977?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24244271$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Menendez, Pablo</contributor><creatorcontrib>Conforti, Antonella</creatorcontrib><creatorcontrib>Biagini, Simone</creatorcontrib><creatorcontrib>Del Bufalo, Francesca</creatorcontrib><creatorcontrib>Sirleto, Pietro</creatorcontrib><creatorcontrib>Angioni, Adriano</creatorcontrib><creatorcontrib>Starc, Nadia</creatorcontrib><creatorcontrib>Li Pira, Giuseppina</creatorcontrib><creatorcontrib>Moretta, Francesca</creatorcontrib><creatorcontrib>Proia, Alessandra</creatorcontrib><creatorcontrib>Contoli, Benedetta</creatorcontrib><creatorcontrib>Genovese, Silvia</creatorcontrib><creatorcontrib>Ciardi, Claudia</creatorcontrib><creatorcontrib>Avanzini, Maria Antonietta</creatorcontrib><creatorcontrib>Rosti, Vittorio</creatorcontrib><creatorcontrib>Lo-Coco, Francesco</creatorcontrib><creatorcontrib>Locatelli, Franco</creatorcontrib><creatorcontrib>Bernardo, Maria Ester</creatorcontrib><title>Biological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>Abnormalities</subject><subject>Acute lymphoblastic leukemia</subject><subject>Acute lymphocytic leukemia</subject><subject>Adolescent</subject><subject>Analysis</subject><subject>Anemia</subject><subject>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</subject><subject>Blood diseases</subject><subject>Bone marrow</subject><subject>Bone Marrow Cells - metabolism</subject><subject>Bone Marrow Cells - pathology</subject><subject>Cancer</subject><subject>Cell culture</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell proliferation</subject><subject>Cells, Cultured</subject><subject>Chemotherapy</subject><subject>Child</subject><subject>Child health</subject><subject>Child, Preschool</subject><subject>Children & youth</subject><subject>Chromosomes</subject><subject>Cytogenetics</subject><subject>Diagnosis</subject><subject>Differentiation</subject><subject>Disease</subject><subject>Genetic abnormalities</subject><subject>Genetic aspects</subject><subject>Genetics</subject><subject>Hematology</subject><subject>Hematopoiesis</subject><subject>Hematopoiesis - drug effects</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunomodulation</subject><subject>Infant</subject><subject>Laboratories</subject><subject>Leukemia</subject><subject>Lymphatic leukemia</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Medical research</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stromal Cells - metabolism</subject><subject>Mesenchymal Stromal Cells - pathology</subject><subject>Mesenchyme</subject><subject>Morphology</subject><subject>Oncology</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology</subject><subject>Stem cells</subject><subject>Stromal cells</subject><subject>T cells</subject><subject>Time 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functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-89ef69d2a98acfecc8d5976b39e99c880a660a0cb9910fc3e866021a66475fbc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Abnormalities</topic><topic>Acute lymphoblastic leukemia</topic><topic>Acute lymphocytic leukemia</topic><topic>Adolescent</topic><topic>Analysis</topic><topic>Anemia</topic><topic>Antineoplastic 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Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI 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<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> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2013-11, Vol.8 (11), p.e76989 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1449331977 |
source | PubMed Central Free; Publicly Available Content Database |
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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