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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/88536
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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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1844613512276475904 |
score |
13.070432 |