IMT504, the prototype of the immunostimulatory oligonucleotides of the PyNTTTTGT class, increases the number of progenitors of mesenchymal stem cells both in vitro and in vivo: pot...

Autores
Hernando Insúa, Andrés; Montaner, Alejandro Daniel; Rodriguez, Juan Manuel; Elías, Fernanda; Fló, Juan; López, Ricardo A.; Zorzopulos, Ricardo A.; Hofer, Erica L.; Chasseing, Norma Alejandra
Año de publicación
2007
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Bone marrow (BM)-derived adult mesenchymal stem cells (MSCs) have the capacity to differentiate in vitro into different cell lines. This makes them a likely source for application in tissue repair therapies. Here, we report evidence indicating that, both in vivo and in vitro, IMT504, the prototype of the PyNTTTTGT class of immunostimulatory oligonucleotides, significantly increases the number of fibroblast colony-forming units (CFU-Fs) that originate MSCs. When rat BM cells were cultured with IMT504, the mean number of CFU-Fs increased about three times as compared with untreated controls (CFU-F: 19 +/- 6.3 vs. 6.8 +/- 2.0/2 x 10(6) seeded BM cells, p = .03). Furthermore, rats inoculated with IMT504 had a significantly higher number of CFU-Fs both in BM (CFU-F: 124 +/- 33 vs. 38 +/- 17/femur, p = .04) and in peripheral blood (animals with detectable CFU-Fs in circulation 8/12 vs. 2/12, p = .04) as compared with untreated animals. On the other hand, BM-derived adherent cells either treated in vitro with IMT504 or obtained from animals injected with IMT504 possess the capacity to differentiate to the osteogenic and adipogenic cell lineages as regular MSCs. Finally, we found that repair of a bone defect was accelerated in rats injected with IMT504 as compared with control animals (area with consolidated bone: 80% +/- 6.4% vs. 49% +/- 3.5%, p = .03, n = 10 rats per group). Importantly, when two human BM were cultured in the presence of IMT504, the mean number of fibroblastic adherent colonies also increased as compared with controls. These results suggest the possibility of clinical use of IMT504 in bone, and presumably other, tissue repair therapies.
Fil: Hernando Insúa, Andrés. Immunotech S.a.; Argentina
Fil: Montaner, Alejandro Daniel. Fundación Pablo Cassara; Argentina
Fil: Rodriguez, Juan Manuel. Immunotech S.a.; Argentina
Fil: Elías, Fernanda. Immunotech S.a.; Argentina
Fil: Fló, Juan. Immunotech S.a.; Argentina
Fil: López, Ricardo A.. Immunotech S.a.; Argentina
Fil: Zorzopulos, Ricardo A.. Immunotech S.a.; Argentina
Fil: Hofer, Erica L.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Chasseing, Norma Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Materia
Mesenchymal Stem Cells
Imt504
Non-Cpg Oligonucleotides
Tissue Repair Therapy
Leucocytes
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:11336/42069

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oai_identifier_str oai:ri.conicet.gov.ar:11336/42069
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling IMT504, the prototype of the immunostimulatory oligonucleotides of the PyNTTTTGT class, increases the number of progenitors of mesenchymal stem cells both in vitro and in vivo: potential use in tissue repair therapyHernando Insúa, AndrésMontaner, Alejandro DanielRodriguez, Juan ManuelElías, FernandaFló, JuanLópez, Ricardo A.Zorzopulos, Ricardo A.Hofer, Erica L.Chasseing, Norma AlejandraMesenchymal Stem CellsImt504Non-Cpg OligonucleotidesTissue Repair TherapyLeucocyteshttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Bone marrow (BM)-derived adult mesenchymal stem cells (MSCs) have the capacity to differentiate in vitro into different cell lines. This makes them a likely source for application in tissue repair therapies. Here, we report evidence indicating that, both in vivo and in vitro, IMT504, the prototype of the PyNTTTTGT class of immunostimulatory oligonucleotides, significantly increases the number of fibroblast colony-forming units (CFU-Fs) that originate MSCs. When rat BM cells were cultured with IMT504, the mean number of CFU-Fs increased about three times as compared with untreated controls (CFU-F: 19 +/- 6.3 vs. 6.8 +/- 2.0/2 x 10(6) seeded BM cells, p = .03). Furthermore, rats inoculated with IMT504 had a significantly higher number of CFU-Fs both in BM (CFU-F: 124 +/- 33 vs. 38 +/- 17/femur, p = .04) and in peripheral blood (animals with detectable CFU-Fs in circulation 8/12 vs. 2/12, p = .04) as compared with untreated animals. On the other hand, BM-derived adherent cells either treated in vitro with IMT504 or obtained from animals injected with IMT504 possess the capacity to differentiate to the osteogenic and adipogenic cell lineages as regular MSCs. Finally, we found that repair of a bone defect was accelerated in rats injected with IMT504 as compared with control animals (area with consolidated bone: 80% +/- 6.4% vs. 49% +/- 3.5%, p = .03, n = 10 rats per group). Importantly, when two human BM were cultured in the presence of IMT504, the mean number of fibroblastic adherent colonies also increased as compared with controls. These results suggest the possibility of clinical use of IMT504 in bone, and presumably other, tissue repair therapies.Fil: Hernando Insúa, Andrés. Immunotech S.a.; ArgentinaFil: Montaner, Alejandro Daniel. Fundación Pablo Cassara; ArgentinaFil: Rodriguez, Juan Manuel. Immunotech S.a.; ArgentinaFil: Elías, Fernanda. Immunotech S.a.; ArgentinaFil: Fló, Juan. Immunotech S.a.; ArgentinaFil: López, Ricardo A.. Immunotech S.a.; ArgentinaFil: Zorzopulos, Ricardo A.. Immunotech S.a.; ArgentinaFil: Hofer, Erica L.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Chasseing, Norma Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaAlphamed Press2007-04-25info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/42069Hernando Insúa, Andrés; Montaner, Alejandro Daniel; Rodriguez, Juan Manuel; Elías, Fernanda; Fló, Juan; et al.; IMT504, the prototype of the immunostimulatory oligonucleotides of the PyNTTTTGT class, increases the number of progenitors of mesenchymal stem cells both in vitro and in vivo: potential use in tissue repair therapy; Alphamed Press; Stem Cells; 25; 4; 25-4-2007; 1047-10541066-50991549-4918CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://stemcellsjournals.onlinelibrary.wiley.com/doi/abs/10.1634/stemcells.2006-0479info:eu-repo/semantics/altIdentifier/doi/10.1634/stemcells.2006-0479info:eu-repo/semantics/altIdentifier/pmid/17420228info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:47:35Zoai:ri.conicet.gov.ar:11336/42069instacron: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:34982025-09-03 09:47:35.342CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv IMT504, the prototype of the immunostimulatory oligonucleotides of the PyNTTTTGT class, increases the number of progenitors of mesenchymal stem cells both in vitro and in vivo: potential use in tissue repair therapy
title IMT504, the prototype of the immunostimulatory oligonucleotides of the PyNTTTTGT class, increases the number of progenitors of mesenchymal stem cells both in vitro and in vivo: potential use in tissue repair therapy
spellingShingle IMT504, the prototype of the immunostimulatory oligonucleotides of the PyNTTTTGT class, increases the number of progenitors of mesenchymal stem cells both in vitro and in vivo: potential use in tissue repair therapy
Hernando Insúa, Andrés
Mesenchymal Stem Cells
Imt504
Non-Cpg Oligonucleotides
Tissue Repair Therapy
Leucocytes
title_short IMT504, the prototype of the immunostimulatory oligonucleotides of the PyNTTTTGT class, increases the number of progenitors of mesenchymal stem cells both in vitro and in vivo: potential use in tissue repair therapy
title_full IMT504, the prototype of the immunostimulatory oligonucleotides of the PyNTTTTGT class, increases the number of progenitors of mesenchymal stem cells both in vitro and in vivo: potential use in tissue repair therapy
title_fullStr IMT504, the prototype of the immunostimulatory oligonucleotides of the PyNTTTTGT class, increases the number of progenitors of mesenchymal stem cells both in vitro and in vivo: potential use in tissue repair therapy
title_full_unstemmed IMT504, the prototype of the immunostimulatory oligonucleotides of the PyNTTTTGT class, increases the number of progenitors of mesenchymal stem cells both in vitro and in vivo: potential use in tissue repair therapy
title_sort IMT504, the prototype of the immunostimulatory oligonucleotides of the PyNTTTTGT class, increases the number of progenitors of mesenchymal stem cells both in vitro and in vivo: potential use in tissue repair therapy
dc.creator.none.fl_str_mv Hernando Insúa, Andrés
Montaner, Alejandro Daniel
Rodriguez, Juan Manuel
Elías, Fernanda
Fló, Juan
López, Ricardo A.
Zorzopulos, Ricardo A.
Hofer, Erica L.
Chasseing, Norma Alejandra
author Hernando Insúa, Andrés
author_facet Hernando Insúa, Andrés
Montaner, Alejandro Daniel
Rodriguez, Juan Manuel
Elías, Fernanda
Fló, Juan
López, Ricardo A.
Zorzopulos, Ricardo A.
Hofer, Erica L.
Chasseing, Norma Alejandra
author_role author
author2 Montaner, Alejandro Daniel
Rodriguez, Juan Manuel
Elías, Fernanda
Fló, Juan
López, Ricardo A.
Zorzopulos, Ricardo A.
Hofer, Erica L.
Chasseing, Norma Alejandra
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Mesenchymal Stem Cells
Imt504
Non-Cpg Oligonucleotides
Tissue Repair Therapy
Leucocytes
topic Mesenchymal Stem Cells
Imt504
Non-Cpg Oligonucleotides
Tissue Repair Therapy
Leucocytes
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Bone marrow (BM)-derived adult mesenchymal stem cells (MSCs) have the capacity to differentiate in vitro into different cell lines. This makes them a likely source for application in tissue repair therapies. Here, we report evidence indicating that, both in vivo and in vitro, IMT504, the prototype of the PyNTTTTGT class of immunostimulatory oligonucleotides, significantly increases the number of fibroblast colony-forming units (CFU-Fs) that originate MSCs. When rat BM cells were cultured with IMT504, the mean number of CFU-Fs increased about three times as compared with untreated controls (CFU-F: 19 +/- 6.3 vs. 6.8 +/- 2.0/2 x 10(6) seeded BM cells, p = .03). Furthermore, rats inoculated with IMT504 had a significantly higher number of CFU-Fs both in BM (CFU-F: 124 +/- 33 vs. 38 +/- 17/femur, p = .04) and in peripheral blood (animals with detectable CFU-Fs in circulation 8/12 vs. 2/12, p = .04) as compared with untreated animals. On the other hand, BM-derived adherent cells either treated in vitro with IMT504 or obtained from animals injected with IMT504 possess the capacity to differentiate to the osteogenic and adipogenic cell lineages as regular MSCs. Finally, we found that repair of a bone defect was accelerated in rats injected with IMT504 as compared with control animals (area with consolidated bone: 80% +/- 6.4% vs. 49% +/- 3.5%, p = .03, n = 10 rats per group). Importantly, when two human BM were cultured in the presence of IMT504, the mean number of fibroblastic adherent colonies also increased as compared with controls. These results suggest the possibility of clinical use of IMT504 in bone, and presumably other, tissue repair therapies.
Fil: Hernando Insúa, Andrés. Immunotech S.a.; Argentina
Fil: Montaner, Alejandro Daniel. Fundación Pablo Cassara; Argentina
Fil: Rodriguez, Juan Manuel. Immunotech S.a.; Argentina
Fil: Elías, Fernanda. Immunotech S.a.; Argentina
Fil: Fló, Juan. Immunotech S.a.; Argentina
Fil: López, Ricardo A.. Immunotech S.a.; Argentina
Fil: Zorzopulos, Ricardo A.. Immunotech S.a.; Argentina
Fil: Hofer, Erica L.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Chasseing, Norma Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
description Bone marrow (BM)-derived adult mesenchymal stem cells (MSCs) have the capacity to differentiate in vitro into different cell lines. This makes them a likely source for application in tissue repair therapies. Here, we report evidence indicating that, both in vivo and in vitro, IMT504, the prototype of the PyNTTTTGT class of immunostimulatory oligonucleotides, significantly increases the number of fibroblast colony-forming units (CFU-Fs) that originate MSCs. When rat BM cells were cultured with IMT504, the mean number of CFU-Fs increased about three times as compared with untreated controls (CFU-F: 19 +/- 6.3 vs. 6.8 +/- 2.0/2 x 10(6) seeded BM cells, p = .03). Furthermore, rats inoculated with IMT504 had a significantly higher number of CFU-Fs both in BM (CFU-F: 124 +/- 33 vs. 38 +/- 17/femur, p = .04) and in peripheral blood (animals with detectable CFU-Fs in circulation 8/12 vs. 2/12, p = .04) as compared with untreated animals. On the other hand, BM-derived adherent cells either treated in vitro with IMT504 or obtained from animals injected with IMT504 possess the capacity to differentiate to the osteogenic and adipogenic cell lineages as regular MSCs. Finally, we found that repair of a bone defect was accelerated in rats injected with IMT504 as compared with control animals (area with consolidated bone: 80% +/- 6.4% vs. 49% +/- 3.5%, p = .03, n = 10 rats per group). Importantly, when two human BM were cultured in the presence of IMT504, the mean number of fibroblastic adherent colonies also increased as compared with controls. These results suggest the possibility of clinical use of IMT504 in bone, and presumably other, tissue repair therapies.
publishDate 2007
dc.date.none.fl_str_mv 2007-04-25
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/11336/42069
Hernando Insúa, Andrés; Montaner, Alejandro Daniel; Rodriguez, Juan Manuel; Elías, Fernanda; Fló, Juan; et al.; IMT504, the prototype of the immunostimulatory oligonucleotides of the PyNTTTTGT class, increases the number of progenitors of mesenchymal stem cells both in vitro and in vivo: potential use in tissue repair therapy; Alphamed Press; Stem Cells; 25; 4; 25-4-2007; 1047-1054
1066-5099
1549-4918
CONICET Digital
CONICET
url http://hdl.handle.net/11336/42069
identifier_str_mv Hernando Insúa, Andrés; Montaner, Alejandro Daniel; Rodriguez, Juan Manuel; Elías, Fernanda; Fló, Juan; et al.; IMT504, the prototype of the immunostimulatory oligonucleotides of the PyNTTTTGT class, increases the number of progenitors of mesenchymal stem cells both in vitro and in vivo: potential use in tissue repair therapy; Alphamed Press; Stem Cells; 25; 4; 25-4-2007; 1047-1054
1066-5099
1549-4918
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://stemcellsjournals.onlinelibrary.wiley.com/doi/abs/10.1634/stemcells.2006-0479
info:eu-repo/semantics/altIdentifier/doi/10.1634/stemcells.2006-0479
info:eu-repo/semantics/altIdentifier/pmid/17420228
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
dc.publisher.none.fl_str_mv Alphamed Press
publisher.none.fl_str_mv Alphamed Press
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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