The low viability of human CD34+ cells under acidic conditions is improved by exposure to thrombopoietin, stem cell factor, interleukin‐3, or increased cyclic adenosine monophospha...

Autores
D'Atri, Lina Paola; Etulain, Julia; Romaniuk, María Albertina; Torres, Oscar; Negrotto, Soledad; Schattner, Mirta Ana
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
BACKGROUND: Transplanted hematopoietic progenitor cells (CD34+) have shown great promise in regenerative medicine. However, the therapeutic potential of transplanted cells is limited by their poor viability. It is well known that the microenvironment in which progenitors reside substantially affects their behavior. Because extracellular acidosis is a common feature of injured tissues or the tumor microenvironment and is a critical regulator of cell survival and activation, we evaluated the impact of acidosis on CD34+ cell biology. STUDY DESIGN AND METHODS: Apoptosis was evaluated by fluorescence microscopy and binding of annexin V, hypodiploid cells, Bcl-xL expression, active caspase-3, and mitochondrial membrane potential was determined by flow cytometry. Colony-forming units were studied by clonogenic assays, and cell cycle was evaluated by flow cytometry. RESULTS: Exposure of CD34+ cells to low pH (7.0-6.5) caused intracellular acidification, decreased cell proliferation, and triggered apoptosis via the mitochondrial pathway. Whereas exposure to thrombopoietin (TPO), stem cell factor (SCF), interleukin (IL)-3 or increases in cyclic adenosine monophosphate (cAMP) levels prevented CD34+ cell death induced by acidic conditions, granulocyte-macrophage?colony-stimulating factor, FMS-like tyrosine kinase 3-ligand, erythropoietin, and vascular endothelial growth factor had no effect. Despite their cytoprotective effect, CD34+ cell expansion triggered by TPO, SCF, or IL-3 was significantly impaired at low pH. However, a cocktail of these three cytokines synergistically supported proliferation, cell cycle progression, and colony formation. DISCUSSION: Our findings indicate that an acidic milieu is deleterious for CD34+ cells and that a combination of certain cytokines and cAMP donors may improve cell viability and function. These data may be useful to develop new therapeutic strategies or to optimize protocols for regenerative medicine.
Fil: D'Atri, Lina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina
Fil: Etulain, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina
Fil: Romaniuk, María Albertina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Torres, Oscar. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina
Fil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina
Fil: Schattner, Mirta Ana. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Materia
CD34 cells
Acidosis
thrombopoietin
Interleukin-3
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/278237
Acceder
id CONICETDig_5ed1d64dfb71e0750fc8d1f352e39694
oai_identifier_str oai:ri.conicet.gov.ar:11336/278237
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The low viability of human CD34+ cells under acidic conditions is improved by exposure to thrombopoietin, stem cell factor, interleukin‐3, or increased cyclic adenosine monophosphate levelsD'Atri, Lina PaolaEtulain, JuliaRomaniuk, María AlbertinaTorres, OscarNegrotto, SoledadSchattner, Mirta AnaCD34 cellsAcidosisthrombopoietinInterleukin-3https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1BACKGROUND: Transplanted hematopoietic progenitor cells (CD34+) have shown great promise in regenerative medicine. However, the therapeutic potential of transplanted cells is limited by their poor viability. It is well known that the microenvironment in which progenitors reside substantially affects their behavior. Because extracellular acidosis is a common feature of injured tissues or the tumor microenvironment and is a critical regulator of cell survival and activation, we evaluated the impact of acidosis on CD34+ cell biology. STUDY DESIGN AND METHODS: Apoptosis was evaluated by fluorescence microscopy and binding of annexin V, hypodiploid cells, Bcl-xL expression, active caspase-3, and mitochondrial membrane potential was determined by flow cytometry. Colony-forming units were studied by clonogenic assays, and cell cycle was evaluated by flow cytometry. RESULTS: Exposure of CD34+ cells to low pH (7.0-6.5) caused intracellular acidification, decreased cell proliferation, and triggered apoptosis via the mitochondrial pathway. Whereas exposure to thrombopoietin (TPO), stem cell factor (SCF), interleukin (IL)-3 or increases in cyclic adenosine monophosphate (cAMP) levels prevented CD34+ cell death induced by acidic conditions, granulocyte-macrophage?colony-stimulating factor, FMS-like tyrosine kinase 3-ligand, erythropoietin, and vascular endothelial growth factor had no effect. Despite their cytoprotective effect, CD34+ cell expansion triggered by TPO, SCF, or IL-3 was significantly impaired at low pH. However, a cocktail of these three cytokines synergistically supported proliferation, cell cycle progression, and colony formation. DISCUSSION: Our findings indicate that an acidic milieu is deleterious for CD34+ cells and that a combination of certain cytokines and cAMP donors may improve cell viability and function. These data may be useful to develop new therapeutic strategies or to optimize protocols for regenerative medicine.Fil: D'Atri, Lina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; ArgentinaFil: Etulain, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; ArgentinaFil: Romaniuk, María Albertina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Torres, Oscar. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; ArgentinaFil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; ArgentinaFil: Schattner, Mirta Ana. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaWiley Blackwell Publishing, Inc2011-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/278237D'Atri, Lina Paola; Etulain, Julia; Romaniuk, María Albertina; Torres, Oscar; Negrotto, Soledad; et al.; The low viability of human CD34+ cells under acidic conditions is improved by exposure to thrombopoietin, stem cell factor, interleukin‐3, or increased cyclic adenosine monophosphate levels; Wiley Blackwell Publishing, Inc; Transfusion; 51; 8; 2-2011; 1784-17950041-1132CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1111/j.1537-2995.2010.03051.xinfo:eu-repo/semantics/altIdentifier/doi/10.1111/j.1537-2995.2010.03051.xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-23T14:46:16Zoai:ri.conicet.gov.ar:11336/278237instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-12-23 14:46:16.573CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The low viability of human CD34+ cells under acidic conditions is improved by exposure to thrombopoietin, stem cell factor, interleukin‐3, or increased cyclic adenosine monophosphate levels
title The low viability of human CD34+ cells under acidic conditions is improved by exposure to thrombopoietin, stem cell factor, interleukin‐3, or increased cyclic adenosine monophosphate levels
spellingShingle The low viability of human CD34+ cells under acidic conditions is improved by exposure to thrombopoietin, stem cell factor, interleukin‐3, or increased cyclic adenosine monophosphate levels
D'Atri, Lina Paola
CD34 cells
Acidosis
thrombopoietin
Interleukin-3
title_short The low viability of human CD34+ cells under acidic conditions is improved by exposure to thrombopoietin, stem cell factor, interleukin‐3, or increased cyclic adenosine monophosphate levels
title_full The low viability of human CD34+ cells under acidic conditions is improved by exposure to thrombopoietin, stem cell factor, interleukin‐3, or increased cyclic adenosine monophosphate levels
title_fullStr The low viability of human CD34+ cells under acidic conditions is improved by exposure to thrombopoietin, stem cell factor, interleukin‐3, or increased cyclic adenosine monophosphate levels
title_full_unstemmed The low viability of human CD34+ cells under acidic conditions is improved by exposure to thrombopoietin, stem cell factor, interleukin‐3, or increased cyclic adenosine monophosphate levels
title_sort The low viability of human CD34+ cells under acidic conditions is improved by exposure to thrombopoietin, stem cell factor, interleukin‐3, or increased cyclic adenosine monophosphate levels
dc.creator.none.fl_str_mv D'Atri, Lina Paola
Etulain, Julia
Romaniuk, María Albertina
Torres, Oscar
Negrotto, Soledad
Schattner, Mirta Ana
author D'Atri, Lina Paola
author_facet D'Atri, Lina Paola
Etulain, Julia
Romaniuk, María Albertina
Torres, Oscar
Negrotto, Soledad
Schattner, Mirta Ana
author_role author
author2 Etulain, Julia
Romaniuk, María Albertina
Torres, Oscar
Negrotto, Soledad
Schattner, Mirta Ana
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv CD34 cells
Acidosis
thrombopoietin
Interleukin-3
topic CD34 cells
Acidosis
thrombopoietin
Interleukin-3
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv BACKGROUND: Transplanted hematopoietic progenitor cells (CD34+) have shown great promise in regenerative medicine. However, the therapeutic potential of transplanted cells is limited by their poor viability. It is well known that the microenvironment in which progenitors reside substantially affects their behavior. Because extracellular acidosis is a common feature of injured tissues or the tumor microenvironment and is a critical regulator of cell survival and activation, we evaluated the impact of acidosis on CD34+ cell biology. STUDY DESIGN AND METHODS: Apoptosis was evaluated by fluorescence microscopy and binding of annexin V, hypodiploid cells, Bcl-xL expression, active caspase-3, and mitochondrial membrane potential was determined by flow cytometry. Colony-forming units were studied by clonogenic assays, and cell cycle was evaluated by flow cytometry. RESULTS: Exposure of CD34+ cells to low pH (7.0-6.5) caused intracellular acidification, decreased cell proliferation, and triggered apoptosis via the mitochondrial pathway. Whereas exposure to thrombopoietin (TPO), stem cell factor (SCF), interleukin (IL)-3 or increases in cyclic adenosine monophosphate (cAMP) levels prevented CD34+ cell death induced by acidic conditions, granulocyte-macrophage?colony-stimulating factor, FMS-like tyrosine kinase 3-ligand, erythropoietin, and vascular endothelial growth factor had no effect. Despite their cytoprotective effect, CD34+ cell expansion triggered by TPO, SCF, or IL-3 was significantly impaired at low pH. However, a cocktail of these three cytokines synergistically supported proliferation, cell cycle progression, and colony formation. DISCUSSION: Our findings indicate that an acidic milieu is deleterious for CD34+ cells and that a combination of certain cytokines and cAMP donors may improve cell viability and function. These data may be useful to develop new therapeutic strategies or to optimize protocols for regenerative medicine.
Fil: D'Atri, Lina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina
Fil: Etulain, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina
Fil: Romaniuk, María Albertina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Torres, Oscar. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina
Fil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina
Fil: Schattner, Mirta Ana. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
description BACKGROUND: Transplanted hematopoietic progenitor cells (CD34+) have shown great promise in regenerative medicine. However, the therapeutic potential of transplanted cells is limited by their poor viability. It is well known that the microenvironment in which progenitors reside substantially affects their behavior. Because extracellular acidosis is a common feature of injured tissues or the tumor microenvironment and is a critical regulator of cell survival and activation, we evaluated the impact of acidosis on CD34+ cell biology. STUDY DESIGN AND METHODS: Apoptosis was evaluated by fluorescence microscopy and binding of annexin V, hypodiploid cells, Bcl-xL expression, active caspase-3, and mitochondrial membrane potential was determined by flow cytometry. Colony-forming units were studied by clonogenic assays, and cell cycle was evaluated by flow cytometry. RESULTS: Exposure of CD34+ cells to low pH (7.0-6.5) caused intracellular acidification, decreased cell proliferation, and triggered apoptosis via the mitochondrial pathway. Whereas exposure to thrombopoietin (TPO), stem cell factor (SCF), interleukin (IL)-3 or increases in cyclic adenosine monophosphate (cAMP) levels prevented CD34+ cell death induced by acidic conditions, granulocyte-macrophage?colony-stimulating factor, FMS-like tyrosine kinase 3-ligand, erythropoietin, and vascular endothelial growth factor had no effect. Despite their cytoprotective effect, CD34+ cell expansion triggered by TPO, SCF, or IL-3 was significantly impaired at low pH. However, a cocktail of these three cytokines synergistically supported proliferation, cell cycle progression, and colony formation. DISCUSSION: Our findings indicate that an acidic milieu is deleterious for CD34+ cells and that a combination of certain cytokines and cAMP donors may improve cell viability and function. These data may be useful to develop new therapeutic strategies or to optimize protocols for regenerative medicine.
publishDate 2011
dc.date.none.fl_str_mv 2011-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/278237
D'Atri, Lina Paola; Etulain, Julia; Romaniuk, María Albertina; Torres, Oscar; Negrotto, Soledad; et al.; The low viability of human CD34+ cells under acidic conditions is improved by exposure to thrombopoietin, stem cell factor, interleukin‐3, or increased cyclic adenosine monophosphate levels; Wiley Blackwell Publishing, Inc; Transfusion; 51; 8; 2-2011; 1784-1795
0041-1132
CONICET Digital
CONICET
url http://hdl.handle.net/11336/278237
identifier_str_mv D'Atri, Lina Paola; Etulain, Julia; Romaniuk, María Albertina; Torres, Oscar; Negrotto, Soledad; et al.; The low viability of human CD34+ cells under acidic conditions is improved by exposure to thrombopoietin, stem cell factor, interleukin‐3, or increased cyclic adenosine monophosphate levels; Wiley Blackwell Publishing, Inc; Transfusion; 51; 8; 2-2011; 1784-1795
0041-1132
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1111/j.1537-2995.2010.03051.x
info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1537-2995.2010.03051.x
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.952241

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