Publicação
Pre-conditioning with IFN-γ and hypoxia enhances the angiogenic potential of iPSC-Derived MSC secretome
| Resumo: | Induced pluripotent stem cell (iPSC) derived mesenchymal stem cells (iMSCs) represent a promising source of progenitor cells for approaches in the field of bone regeneration. Bone formation is a multi-step process in which osteogenesis and angiogenesis are both involved. Many reports show that the secretome of mesenchymal stromal stem cells (MSCs) influences the microenvironment upon injury, promoting cytoprotection, angiogenesis, and tissue repair of the damaged area. However, the effects of iPSC-derived MSCs secretome on angiogenesis have seldom been investigated. In the present study, the angiogenic properties of IFN-γ pre-conditioned iMSC secretomes were analyzed. We detected a higher expression of the pro-angiogenic genes and proteins of iMSCs and their secretome under IFN-γ and hypoxic stimulation (IFN-H). Tube formation and wound healing assays revealed a higher angiogenic potential of HUVECs in the presence of IFN-γ conditioned iMSC secretome. Sprouting assays demonstrated that within Coll/HA scaffolds, HUVECs spheroids formed significantly more and longer sprouts in the presence of IFN-γ conditioned iMSC secretome. Through gene expression analyses, pro-angiogenic genes (FLT-1, KDR, MET, TIMP-1, HIF-1α, IL-8, and VCAM-1) in HUVECs showed a significant up-regulation and down-regulation of two anti-angiogenic genes (TIMP-4 and IGFBP-1) compared to the data obtained in the other groups. Our results demonstrate that the iMSC secretome, pre-conditioned under inflammatory and hypoxic conditions, induced the highest angiogenic properties of HUVECs. We conclude that pre-activated iMSCs enhance their efficacy and represent a suitable cell source for collagen/hydroxyapatite with angiogenic properties. |
|---|---|
| Autores principais: | Wang, Suya |
| Outros Autores: | Umrath, Felix; Cen, Wanjing; Salgado, A. J.; Reinert, Siegmar; Alexander, Dorothea |
| Assunto: | iPSC-derived MSCs iMSC secretome Pre-conditioning Angiogenesis IFN-γ Hypoxia Potentiation of iMSC efficacy IFN-gamma |
| Ano: | 2022 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1867438526675550208 |
|---|---|
| author | Wang, Suya |
| author2 | Umrath, Felix Cen, Wanjing Salgado, A. J. Reinert, Siegmar Alexander, Dorothea |
| author2_role | author author author author author |
| author_facet | Wang, Suya Umrath, Felix Cen, Wanjing Salgado, A. J. Reinert, Siegmar Alexander, Dorothea |
| author_role | author |
| contributor_name_str_mv | RepositóriUM - Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Wang, Suya\"},{\"Person.name\":\"Umrath, Felix\"},{\"Person.name\":\"Cen, Wanjing\"},{\"Person.name\":\"Salgado, A. J.\"},{\"Person.name\":\"Reinert, Siegmar\"},{\"Person.name\":\"Alexander, Dorothea\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | RepositóriUM - Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Wang, Suya Umrath, Felix Cen, Wanjing Salgado, A. J. Reinert, Siegmar Alexander, Dorothea |
| datacite.date.Accepted.fl_str_mv | 2022-03-14T00:00:00Z |
| datacite.date.available.fl_str_mv | 2022-09-19T09:53:46Z |
| datacite.date.embargoed.fl_str_mv | 2022-09-19T09:53:46Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | iPSC-derived MSCs iMSC secretome Pre-conditioning Angiogenesis IFN-γ Hypoxia Potentiation of iMSC efficacy IFN-gamma |
| datacite.titles.title.fl_str_mv | Pre-conditioning with IFN-γ and hypoxia enhances the angiogenic potential of iPSC-Derived MSC secretome |
| dc.contributor.none.fl_str_mv | RepositóriUM - Universidade do Minho |
| dc.creator.none.fl_str_mv | Wang, Suya Umrath, Felix Cen, Wanjing Salgado, A. J. Reinert, Siegmar Alexander, Dorothea |
| dc.date.Accepted.fl_str_mv | 2022-03-14T00:00:00Z |
| dc.date.available.fl_str_mv | 2022-09-19T09:53:46Z |
| dc.date.embargoed.fl_str_mv | 2022-09-19T09:53:46Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/79573 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Multidisciplinary Digital Publishing Institute (MDPI) |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.rights.rights.copyright.fl_str_mv | openAccess |
| dc.subject.none.fl_str_mv | iPSC-derived MSCs iMSC secretome Pre-conditioning Angiogenesis IFN-γ Hypoxia Potentiation of iMSC efficacy IFN-gamma |
| dc.title.fl_str_mv | Pre-conditioning with IFN-γ and hypoxia enhances the angiogenic potential of iPSC-Derived MSC secretome |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Induced pluripotent stem cell (iPSC) derived mesenchymal stem cells (iMSCs) represent a promising source of progenitor cells for approaches in the field of bone regeneration. Bone formation is a multi-step process in which osteogenesis and angiogenesis are both involved. Many reports show that the secretome of mesenchymal stromal stem cells (MSCs) influences the microenvironment upon injury, promoting cytoprotection, angiogenesis, and tissue repair of the damaged area. However, the effects of iPSC-derived MSCs secretome on angiogenesis have seldom been investigated. In the present study, the angiogenic properties of IFN-γ pre-conditioned iMSC secretomes were analyzed. We detected a higher expression of the pro-angiogenic genes and proteins of iMSCs and their secretome under IFN-γ and hypoxic stimulation (IFN-H). Tube formation and wound healing assays revealed a higher angiogenic potential of HUVECs in the presence of IFN-γ conditioned iMSC secretome. Sprouting assays demonstrated that within Coll/HA scaffolds, HUVECs spheroids formed significantly more and longer sprouts in the presence of IFN-γ conditioned iMSC secretome. Through gene expression analyses, pro-angiogenic genes (FLT-1, KDR, MET, TIMP-1, HIF-1α, IL-8, and VCAM-1) in HUVECs showed a significant up-regulation and down-regulation of two anti-angiogenic genes (TIMP-4 and IGFBP-1) compared to the data obtained in the other groups. Our results demonstrate that the iMSC secretome, pre-conditioned under inflammatory and hypoxic conditions, induced the highest angiogenic properties of HUVECs. We conclude that pre-activated iMSCs enhance their efficacy and represent a suitable cell source for collagen/hydroxyapatite with angiogenic properties. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorium.uminho.pt/bitstreams/ce99c21d-bb73-4a0c-a5b3-bef4bd257306/download |
| id | rum_cdce510e5bd97ad60fe4e6ece0db4c5b |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/79573 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/79573 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Wang, Suya Umrath, Felix Cen, Wanjing Salgado, A. J. Reinert, Siegmar Alexander, Dorothea |
| publishDate | 2022 |
| publisher.none.fl_str_mv | Multidisciplinary Digital Publishing Institute (MDPI) |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engMultidisciplinary Digital Publishing Institute (MDPI)porInduced pluripotent stem cell (iPSC) derived mesenchymal stem cells (iMSCs) represent a promising source of progenitor cells for approaches in the field of bone regeneration. Bone formation is a multi-step process in which osteogenesis and angiogenesis are both involved. Many reports show that the secretome of mesenchymal stromal stem cells (MSCs) influences the microenvironment upon injury, promoting cytoprotection, angiogenesis, and tissue repair of the damaged area. However, the effects of iPSC-derived MSCs secretome on angiogenesis have seldom been investigated. In the present study, the angiogenic properties of IFN-γ pre-conditioned iMSC secretomes were analyzed. We detected a higher expression of the pro-angiogenic genes and proteins of iMSCs and their secretome under IFN-γ and hypoxic stimulation (IFN-H). Tube formation and wound healing assays revealed a higher angiogenic potential of HUVECs in the presence of IFN-γ conditioned iMSC secretome. Sprouting assays demonstrated that within Coll/HA scaffolds, HUVECs spheroids formed significantly more and longer sprouts in the presence of IFN-γ conditioned iMSC secretome. Through gene expression analyses, pro-angiogenic genes (FLT-1, KDR, MET, TIMP-1, HIF-1α, IL-8, and VCAM-1) in HUVECs showed a significant up-regulation and down-regulation of two anti-angiogenic genes (TIMP-4 and IGFBP-1) compared to the data obtained in the other groups. Our results demonstrate that the iMSC secretome, pre-conditioned under inflammatory and hypoxic conditions, induced the highest angiogenic properties of HUVECs. We conclude that pre-activated iMSCs enhance their efficacy and represent a suitable cell source for collagen/hydroxyapatite with angiogenic properties.application/pdfporPre-conditioning with IFN-γ and hypoxia enhances the angiogenic potential of iPSC-Derived MSC secretomeWang, SuyaUmrath, FelixCen, WanjingSalgado, A. J.Reinert, SiegmarAlexander, DorotheaHostingInstitutionOrganizationalRepositóriUM - Universidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptCITATIONWang, S.; Umrath, F.; Cen, W.; Salgado, A.J.; Reinert, S.; Alexander, D. Pre-Conditioning with IFN-γ and Hypoxia Enhances the Angiogenic Potential of iPSC-Derived MSC Secretome. Cells 2022, 11, 988. https://doi.org/10.3390/cells11060988PMID35326438ARTICLENUMBER988EISSNIsPartOf2073-4409DOIIsPartOf10.3390/cells110609882022-09-19T09:53:46Z2022-03-142022-03-24T14:47:56Z2022-03-14T00:00:00ZHandlehttps://hdl.handle.net/1822/79573http://purl.org/coar/access_right/c_abf2open accessiPSC-derived MSCsiMSC secretomePre-conditioningAngiogenesisIFN-γHypoxiaPotentiation of iMSC efficacyIFN-gamma3691254 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal article2022-03-14http://creativecommons.org/licenses/by/4.0/openAccesshttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorium.uminho.pt/bitstreams/ce99c21d-bb73-4a0c-a5b3-bef4bd257306/download |
| spellingShingle | Pre-conditioning with IFN-γ and hypoxia enhances the angiogenic potential of iPSC-Derived MSC secretome Wang, Suya iPSC-derived MSCs iMSC secretome Pre-conditioning Angiogenesis IFN-γ Hypoxia Potentiation of iMSC efficacy IFN-gamma |
| status | SINGLETON |
| subject.fl_str_mv | iPSC-derived MSCs iMSC secretome Pre-conditioning Angiogenesis IFN-γ Hypoxia Potentiation of iMSC efficacy IFN-gamma |
| title | Pre-conditioning with IFN-γ and hypoxia enhances the angiogenic potential of iPSC-Derived MSC secretome |
| title_full | Pre-conditioning with IFN-γ and hypoxia enhances the angiogenic potential of iPSC-Derived MSC secretome |
| title_fullStr | Pre-conditioning with IFN-γ and hypoxia enhances the angiogenic potential of iPSC-Derived MSC secretome |
| title_full_unstemmed | Pre-conditioning with IFN-γ and hypoxia enhances the angiogenic potential of iPSC-Derived MSC secretome |
| title_short | Pre-conditioning with IFN-γ and hypoxia enhances the angiogenic potential of iPSC-Derived MSC secretome |
| title_sort | Pre-conditioning with IFN-γ and hypoxia enhances the angiogenic potential of iPSC-Derived MSC secretome |
| topic | iPSC-derived MSCs iMSC secretome Pre-conditioning Angiogenesis IFN-γ Hypoxia Potentiation of iMSC efficacy IFN-gamma |
| topic_facet | iPSC-derived MSCs iMSC secretome Pre-conditioning Angiogenesis IFN-γ Hypoxia Potentiation of iMSC efficacy IFN-gamma |
| url | https://hdl.handle.net/1822/79573 |
| visible | 1 |