Systemically administered allogeneic mesenchymal stem cells do not aggravate the progression of precancerous lesions: A new biosafety insight

Autores
Bruna, Flavia Alejandra; Plaza, Anita; Arango, Martha; Espinoza, Iris; Conget, Paulette
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Mesenchymal stem cells (MSCs) are a heterogeneous subset of stromal cells currently tested for multiple therapeutic purposes. Their potential to home into tumors, to secrete trophic/vasculogenic factors, and to suppress immune response raises questions regarding their biosafety. Our aim was to evaluate whether systemically administered allogeneic MSCs modify the natural progression of precancerous lesions and whether their putative effect depends on cancer stage and/or cell dose. Methods: Oral squamous cell carcinoma (OSCC) was induced in Syrian golden hamsters by topical application of 7,12-dimethylbenz[a]anthracene in one buccal pouch. At hyperplasia, dysplasia, or papilloma stage, animals received intracardially the vehicle or 0.7 × 10 6 , 7 × 10 6 , or 21 × 10 6 allogeneic bone marrow-derived MSCs/kg. OSCC progression was assessed according to the presence of erythroplakia and leukoplakia, extent of inflammation and vascularization, and appearance, volume, and staging of tumors. Also, the homing of donor cells was studied. Results: Precancerous lesions progressed from hyperplasia to dysplasia in 2 weeks, from dysplasia to papilloma in 3 weeks, and from papilloma to carcinoma in 4 weeks. This time course was unmodified by the systemic administration of MSCs at hyperplasia or dysplasia stages. When MSCs were administered at papilloma stage, lesions did not progress to carcinoma stage. Tumors developed in hamsters receiving 0.7 × 10 6 or 7 × 10 6 MSCs/kg at hyperplasia stage were significantly smaller than those found in control animals (25 ± 4 or 23 ± 4 mm 3 versus 72 ± 19 mm 3 , p < 0.05). Similar results were obtained when 0.7 × 10 6 , 7 × 10 6 , or 21 × 10 6 MSCs/kg were administered at papilloma stage (44 ± 15, 28 ± 7, or 28 ± 5 mm 3 versus 104 ± 26 mm 3 , p < 0.05). For dysplasia stage, only the lower concentration of MSCs reached statistical significance (21 ± 9 mm 3 versus 94 ± 39 mm 3 , p < 0.05). Animals receiving 21 × 10 6 MSCs/kg at hyperplasia stage developed tumors larger than those found in animals that received the vehicle (147 ± 47 mm 3 versus 72 ± 19 mm 3 , p < 0.05). Donor cells were rarely found in precancerous lesions. Conclusions: Systemically administered allogeneic MSCs do not aggravate the progression of precancerous lesions. Moreover, they preclude cancer progression and tumor growth.
Fil: Bruna, Flavia Alejandra. Universidad del Desarrollo; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Plaza, Anita. Universidad del Desarrollo; Chile
Fil: Arango, Martha. Universidad del Desarrollo; Chile
Fil: Espinoza, Iris. Universidad de Chile; Chile
Fil: Conget, Paulette. Universidad del Desarrollo; Chile
Materia
BIOSAFETY
CANCER PROGRESSION
MESENCHYMAL STEM CELLS
MULTIPOTENT STROMAL CELLS
ORAL SQUAMOUS CELL CARCINOMA
SYSTEMIC ADMINISTRATION
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:11336/88536

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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Systemically administered allogeneic mesenchymal stem cells do not aggravate the progression of precancerous lesions: A new biosafety insightBruna, Flavia AlejandraPlaza, AnitaArango, MarthaEspinoza, IrisConget, PauletteBIOSAFETYCANCER PROGRESSIONMESENCHYMAL STEM CELLSMULTIPOTENT STROMAL CELLSORAL SQUAMOUS CELL CARCINOMASYSTEMIC ADMINISTRATIONhttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Background: Mesenchymal stem cells (MSCs) are a heterogeneous subset of stromal cells currently tested for multiple therapeutic purposes. Their potential to home into tumors, to secrete trophic/vasculogenic factors, and to suppress immune response raises questions regarding their biosafety. Our aim was to evaluate whether systemically administered allogeneic MSCs modify the natural progression of precancerous lesions and whether their putative effect depends on cancer stage and/or cell dose. Methods: Oral squamous cell carcinoma (OSCC) was induced in Syrian golden hamsters by topical application of 7,12-dimethylbenz[a]anthracene in one buccal pouch. At hyperplasia, dysplasia, or papilloma stage, animals received intracardially the vehicle or 0.7 × 10 6 , 7 × 10 6 , or 21 × 10 6 allogeneic bone marrow-derived MSCs/kg. OSCC progression was assessed according to the presence of erythroplakia and leukoplakia, extent of inflammation and vascularization, and appearance, volume, and staging of tumors. Also, the homing of donor cells was studied. Results: Precancerous lesions progressed from hyperplasia to dysplasia in 2 weeks, from dysplasia to papilloma in 3 weeks, and from papilloma to carcinoma in 4 weeks. This time course was unmodified by the systemic administration of MSCs at hyperplasia or dysplasia stages. When MSCs were administered at papilloma stage, lesions did not progress to carcinoma stage. Tumors developed in hamsters receiving 0.7 × 10 6 or 7 × 10 6 MSCs/kg at hyperplasia stage were significantly smaller than those found in control animals (25 ± 4 or 23 ± 4 mm 3 versus 72 ± 19 mm 3 , p < 0.05). Similar results were obtained when 0.7 × 10 6 , 7 × 10 6 , or 21 × 10 6 MSCs/kg were administered at papilloma stage (44 ± 15, 28 ± 7, or 28 ± 5 mm 3 versus 104 ± 26 mm 3 , p < 0.05). For dysplasia stage, only the lower concentration of MSCs reached statistical significance (21 ± 9 mm 3 versus 94 ± 39 mm 3 , p < 0.05). Animals receiving 21 × 10 6 MSCs/kg at hyperplasia stage developed tumors larger than those found in animals that received the vehicle (147 ± 47 mm 3 versus 72 ± 19 mm 3 , p < 0.05). Donor cells were rarely found in precancerous lesions. Conclusions: Systemically administered allogeneic MSCs do not aggravate the progression of precancerous lesions. Moreover, they preclude cancer progression and tumor growth.Fil: Bruna, Flavia Alejandra. Universidad del Desarrollo; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Plaza, Anita. Universidad del Desarrollo; ChileFil: Arango, Martha. Universidad del Desarrollo; ChileFil: Espinoza, Iris. Universidad de Chile; ChileFil: Conget, Paulette. Universidad del Desarrollo; ChileBioMed Central2018-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/88536Bruna, Flavia Alejandra; Plaza, Anita; Arango, Martha; Espinoza, Iris; Conget, Paulette; Systemically administered allogeneic mesenchymal stem cells do not aggravate the progression of precancerous lesions: A new biosafety insight; BioMed Central; Stem Cell Research and Therapy; 9; 1; 5-2018; 1-101757-6512CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1186/s13287-018-0878-1info:eu-repo/semantics/altIdentifier/url/https://stemcellres.biomedcentral.com/articles/10.1186/s13287-018-0878-1info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:48:43Zoai:ri.conicet.gov.ar:11336/88536instacron: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:34982025-09-29 09:48:43.596CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Systemically administered allogeneic mesenchymal stem cells do not aggravate the progression of precancerous lesions: A new biosafety insight
title Systemically administered allogeneic mesenchymal stem cells do not aggravate the progression of precancerous lesions: A new biosafety insight
spellingShingle Systemically administered allogeneic mesenchymal stem cells do not aggravate the progression of precancerous lesions: A new biosafety insight
Bruna, Flavia Alejandra
BIOSAFETY
CANCER PROGRESSION
MESENCHYMAL STEM CELLS
MULTIPOTENT STROMAL CELLS
ORAL SQUAMOUS CELL CARCINOMA
SYSTEMIC ADMINISTRATION
title_short Systemically administered allogeneic mesenchymal stem cells do not aggravate the progression of precancerous lesions: A new biosafety insight
title_full Systemically administered allogeneic mesenchymal stem cells do not aggravate the progression of precancerous lesions: A new biosafety insight
title_fullStr Systemically administered allogeneic mesenchymal stem cells do not aggravate the progression of precancerous lesions: A new biosafety insight
title_full_unstemmed Systemically administered allogeneic mesenchymal stem cells do not aggravate the progression of precancerous lesions: A new biosafety insight
title_sort Systemically administered allogeneic mesenchymal stem cells do not aggravate the progression of precancerous lesions: A new biosafety insight
dc.creator.none.fl_str_mv Bruna, Flavia Alejandra
Plaza, Anita
Arango, Martha
Espinoza, Iris
Conget, Paulette
author Bruna, Flavia Alejandra
author_facet Bruna, Flavia Alejandra
Plaza, Anita
Arango, Martha
Espinoza, Iris
Conget, Paulette
author_role author
author2 Plaza, Anita
Arango, Martha
Espinoza, Iris
Conget, Paulette
author2_role author
author
author
author
dc.subject.none.fl_str_mv BIOSAFETY
CANCER PROGRESSION
MESENCHYMAL STEM CELLS
MULTIPOTENT STROMAL CELLS
ORAL SQUAMOUS CELL CARCINOMA
SYSTEMIC ADMINISTRATION
topic BIOSAFETY
CANCER PROGRESSION
MESENCHYMAL STEM CELLS
MULTIPOTENT STROMAL CELLS
ORAL SQUAMOUS CELL CARCINOMA
SYSTEMIC ADMINISTRATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Mesenchymal stem cells (MSCs) are a heterogeneous subset of stromal cells currently tested for multiple therapeutic purposes. Their potential to home into tumors, to secrete trophic/vasculogenic factors, and to suppress immune response raises questions regarding their biosafety. Our aim was to evaluate whether systemically administered allogeneic MSCs modify the natural progression of precancerous lesions and whether their putative effect depends on cancer stage and/or cell dose. Methods: Oral squamous cell carcinoma (OSCC) was induced in Syrian golden hamsters by topical application of 7,12-dimethylbenz[a]anthracene in one buccal pouch. At hyperplasia, dysplasia, or papilloma stage, animals received intracardially the vehicle or 0.7 × 10 6 , 7 × 10 6 , or 21 × 10 6 allogeneic bone marrow-derived MSCs/kg. OSCC progression was assessed according to the presence of erythroplakia and leukoplakia, extent of inflammation and vascularization, and appearance, volume, and staging of tumors. Also, the homing of donor cells was studied. Results: Precancerous lesions progressed from hyperplasia to dysplasia in 2 weeks, from dysplasia to papilloma in 3 weeks, and from papilloma to carcinoma in 4 weeks. This time course was unmodified by the systemic administration of MSCs at hyperplasia or dysplasia stages. When MSCs were administered at papilloma stage, lesions did not progress to carcinoma stage. Tumors developed in hamsters receiving 0.7 × 10 6 or 7 × 10 6 MSCs/kg at hyperplasia stage were significantly smaller than those found in control animals (25 ± 4 or 23 ± 4 mm 3 versus 72 ± 19 mm 3 , p < 0.05). Similar results were obtained when 0.7 × 10 6 , 7 × 10 6 , or 21 × 10 6 MSCs/kg were administered at papilloma stage (44 ± 15, 28 ± 7, or 28 ± 5 mm 3 versus 104 ± 26 mm 3 , p < 0.05). For dysplasia stage, only the lower concentration of MSCs reached statistical significance (21 ± 9 mm 3 versus 94 ± 39 mm 3 , p < 0.05). Animals receiving 21 × 10 6 MSCs/kg at hyperplasia stage developed tumors larger than those found in animals that received the vehicle (147 ± 47 mm 3 versus 72 ± 19 mm 3 , p < 0.05). Donor cells were rarely found in precancerous lesions. Conclusions: Systemically administered allogeneic MSCs do not aggravate the progression of precancerous lesions. Moreover, they preclude cancer progression and tumor growth.
Fil: Bruna, Flavia Alejandra. Universidad del Desarrollo; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Plaza, Anita. Universidad del Desarrollo; Chile
Fil: Arango, Martha. Universidad del Desarrollo; Chile
Fil: Espinoza, Iris. Universidad de Chile; Chile
Fil: Conget, Paulette. Universidad del Desarrollo; Chile
description Background: Mesenchymal stem cells (MSCs) are a heterogeneous subset of stromal cells currently tested for multiple therapeutic purposes. Their potential to home into tumors, to secrete trophic/vasculogenic factors, and to suppress immune response raises questions regarding their biosafety. Our aim was to evaluate whether systemically administered allogeneic MSCs modify the natural progression of precancerous lesions and whether their putative effect depends on cancer stage and/or cell dose. Methods: Oral squamous cell carcinoma (OSCC) was induced in Syrian golden hamsters by topical application of 7,12-dimethylbenz[a]anthracene in one buccal pouch. At hyperplasia, dysplasia, or papilloma stage, animals received intracardially the vehicle or 0.7 × 10 6 , 7 × 10 6 , or 21 × 10 6 allogeneic bone marrow-derived MSCs/kg. OSCC progression was assessed according to the presence of erythroplakia and leukoplakia, extent of inflammation and vascularization, and appearance, volume, and staging of tumors. Also, the homing of donor cells was studied. Results: Precancerous lesions progressed from hyperplasia to dysplasia in 2 weeks, from dysplasia to papilloma in 3 weeks, and from papilloma to carcinoma in 4 weeks. This time course was unmodified by the systemic administration of MSCs at hyperplasia or dysplasia stages. When MSCs were administered at papilloma stage, lesions did not progress to carcinoma stage. Tumors developed in hamsters receiving 0.7 × 10 6 or 7 × 10 6 MSCs/kg at hyperplasia stage were significantly smaller than those found in control animals (25 ± 4 or 23 ± 4 mm 3 versus 72 ± 19 mm 3 , p < 0.05). Similar results were obtained when 0.7 × 10 6 , 7 × 10 6 , or 21 × 10 6 MSCs/kg were administered at papilloma stage (44 ± 15, 28 ± 7, or 28 ± 5 mm 3 versus 104 ± 26 mm 3 , p < 0.05). For dysplasia stage, only the lower concentration of MSCs reached statistical significance (21 ± 9 mm 3 versus 94 ± 39 mm 3 , p < 0.05). Animals receiving 21 × 10 6 MSCs/kg at hyperplasia stage developed tumors larger than those found in animals that received the vehicle (147 ± 47 mm 3 versus 72 ± 19 mm 3 , p < 0.05). Donor cells were rarely found in precancerous lesions. Conclusions: Systemically administered allogeneic MSCs do not aggravate the progression of precancerous lesions. Moreover, they preclude cancer progression and tumor growth.
publishDate 2018
dc.date.none.fl_str_mv 2018-05
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/11336/88536
Bruna, Flavia Alejandra; Plaza, Anita; Arango, Martha; Espinoza, Iris; Conget, Paulette; Systemically administered allogeneic mesenchymal stem cells do not aggravate the progression of precancerous lesions: A new biosafety insight; BioMed Central; Stem Cell Research and Therapy; 9; 1; 5-2018; 1-10
1757-6512
CONICET Digital
CONICET
url http://hdl.handle.net/11336/88536
identifier_str_mv Bruna, Flavia Alejandra; Plaza, Anita; Arango, Martha; Espinoza, Iris; Conget, Paulette; Systemically administered allogeneic mesenchymal stem cells do not aggravate the progression of precancerous lesions: A new biosafety insight; BioMed Central; Stem Cell Research and Therapy; 9; 1; 5-2018; 1-10
1757-6512
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1186/s13287-018-0878-1
info:eu-repo/semantics/altIdentifier/url/https://stemcellres.biomedcentral.com/articles/10.1186/s13287-018-0878-1
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
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
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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