Bioactivity and miRNome Profiling of Native Extracellular Vesicles in Human Induced Pluripotent Stem Cell‐Cardiomyocyte Differentiation
Abstract Extracellular vesicles (EV) are an attractive therapy to boost cardiac regeneration. Nevertheless, identification of native EV and corresponding cell platform(s) suitable for therapeutic application, is still a challenge. Here, EV are isolated from key stages of the human induced pluripoten...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202104296 |
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| author | Ana F. Louro Marta A. Paiva Marta R. Oliveira Katharina A. Kasper Paula M. Alves Patrícia Gomes‐Alves Margarida Serra |
| author_facet | Ana F. Louro Marta A. Paiva Marta R. Oliveira Katharina A. Kasper Paula M. Alves Patrícia Gomes‐Alves Margarida Serra |
| author_sort | Ana F. Louro |
| collection | DOAJ |
| description | Abstract Extracellular vesicles (EV) are an attractive therapy to boost cardiac regeneration. Nevertheless, identification of native EV and corresponding cell platform(s) suitable for therapeutic application, is still a challenge. Here, EV are isolated from key stages of the human induced pluripotent stem cell‐cardiomyocyte (hiPSC‐CM) differentiation and maturation, i.e., from hiPSC (hiPSC‐EV), cardiac progenitors, immature and mature cardiomyocytes, with the aim of identifying a promising cell biofactory for EV production, and pinpoint the genetic signatures of bioactive EV. EV secreted by hiPSC and cardiac derivatives show a typical size distribution profile and the expression of specific EV markers. Bioactivity assays show increased tube formation and migration in HUVEC treated with hiPSC‐EV compared to EV from committed cell populations. hiPSC‐EV also significantly increase cell cycle activity of hiPSC‐CM. Global miRNA expression profiles, obtained by small RNA‐seq analysis, corroborate an EV‐miRNA pattern indicative of stem cell to cardiomyocyte specification, confirming that hiPSC‐EV are enriched in pluripotency‐associated miRNA with higher in vitro pro‐angiogenic and pro‐proliferative properties. In particular, a stemness maintenance miRNA cluster upregulated in hiPSC‐EV targets the PTEN/PI3K/AKT pathway, involved in cell proliferation and survival. Overall, the findings validate hiPSC as cell biofactories for EV production for cardiac regenerative applications. |
| first_indexed | 2024-12-12T09:43:35Z |
| format | Article |
| id | doaj.art-bdca1a0721614c5c8befc09f2fced737 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-12T09:43:35Z |
| publishDate | 2022-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-bdca1a0721614c5c8befc09f2fced7372022-12-22T00:28:30ZengWileyAdvanced Science2198-38442022-05-01915n/an/a10.1002/advs.202104296Bioactivity and miRNome Profiling of Native Extracellular Vesicles in Human Induced Pluripotent Stem Cell‐Cardiomyocyte DifferentiationAna F. Louro0Marta A. Paiva1Marta R. Oliveira2Katharina A. Kasper3Paula M. Alves4Patrícia Gomes‐Alves5Margarida Serra6iBET Instituto de Biologia Experimental e Tecnológica Apartado 12 Oeiras 2781‐901 PortugaliBET Instituto de Biologia Experimental e Tecnológica Apartado 12 Oeiras 2781‐901 PortugaliBET Instituto de Biologia Experimental e Tecnológica Apartado 12 Oeiras 2781‐901 PortugaliBET Instituto de Biologia Experimental e Tecnológica Apartado 12 Oeiras 2781‐901 PortugaliBET Instituto de Biologia Experimental e Tecnológica Apartado 12 Oeiras 2781‐901 PortugaliBET Instituto de Biologia Experimental e Tecnológica Apartado 12 Oeiras 2781‐901 PortugaliBET Instituto de Biologia Experimental e Tecnológica Apartado 12 Oeiras 2781‐901 PortugalAbstract Extracellular vesicles (EV) are an attractive therapy to boost cardiac regeneration. Nevertheless, identification of native EV and corresponding cell platform(s) suitable for therapeutic application, is still a challenge. Here, EV are isolated from key stages of the human induced pluripotent stem cell‐cardiomyocyte (hiPSC‐CM) differentiation and maturation, i.e., from hiPSC (hiPSC‐EV), cardiac progenitors, immature and mature cardiomyocytes, with the aim of identifying a promising cell biofactory for EV production, and pinpoint the genetic signatures of bioactive EV. EV secreted by hiPSC and cardiac derivatives show a typical size distribution profile and the expression of specific EV markers. Bioactivity assays show increased tube formation and migration in HUVEC treated with hiPSC‐EV compared to EV from committed cell populations. hiPSC‐EV also significantly increase cell cycle activity of hiPSC‐CM. Global miRNA expression profiles, obtained by small RNA‐seq analysis, corroborate an EV‐miRNA pattern indicative of stem cell to cardiomyocyte specification, confirming that hiPSC‐EV are enriched in pluripotency‐associated miRNA with higher in vitro pro‐angiogenic and pro‐proliferative properties. In particular, a stemness maintenance miRNA cluster upregulated in hiPSC‐EV targets the PTEN/PI3K/AKT pathway, involved in cell proliferation and survival. Overall, the findings validate hiPSC as cell biofactories for EV production for cardiac regenerative applications.https://doi.org/10.1002/advs.202104296cardiac regenerationcell biofactoryextracellular vesiclesmiRNomesmall RNA‐seq |
| spellingShingle | Ana F. Louro Marta A. Paiva Marta R. Oliveira Katharina A. Kasper Paula M. Alves Patrícia Gomes‐Alves Margarida Serra Bioactivity and miRNome Profiling of Native Extracellular Vesicles in Human Induced Pluripotent Stem Cell‐Cardiomyocyte Differentiation Advanced Science cardiac regeneration cell biofactory extracellular vesicles miRNome small RNA‐seq |
| title | Bioactivity and miRNome Profiling of Native Extracellular Vesicles in Human Induced Pluripotent Stem Cell‐Cardiomyocyte Differentiation |
| title_full | Bioactivity and miRNome Profiling of Native Extracellular Vesicles in Human Induced Pluripotent Stem Cell‐Cardiomyocyte Differentiation |
| title_fullStr | Bioactivity and miRNome Profiling of Native Extracellular Vesicles in Human Induced Pluripotent Stem Cell‐Cardiomyocyte Differentiation |
| title_full_unstemmed | Bioactivity and miRNome Profiling of Native Extracellular Vesicles in Human Induced Pluripotent Stem Cell‐Cardiomyocyte Differentiation |
| title_short | Bioactivity and miRNome Profiling of Native Extracellular Vesicles in Human Induced Pluripotent Stem Cell‐Cardiomyocyte Differentiation |
| title_sort | bioactivity and mirnome profiling of native extracellular vesicles in human induced pluripotent stem cell cardiomyocyte differentiation |
| topic | cardiac regeneration cell biofactory extracellular vesicles miRNome small RNA‐seq |
| url | https://doi.org/10.1002/advs.202104296 |
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