A multi-organ, feto-maternal interface organ-on-chip, models pregnancy pathology and is a useful preclinical extracellular vesicle drug trial platform
Pregnant women and their fetuses are often excluded from clinical trials due to missing drug-related pre-clinical trial information at the human feto-maternal interface (FMi). The two interfaces-placenta/decidua and fetal membranes/decidua are gatekeepers of drug transport; however, testing their fu...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-06-01
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| Series: | Extracellular Vesicle |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2773041724000027 |
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| author | Melody Safarzadeh Lauren S. Richardson Ananth Kumar Kammala Angela Mosebarger Mohamed Bettayeb Sungjin Kim Po Yi Lam Enkhtuya Radnaa Arum Han Ramkumar Menon |
| author_facet | Melody Safarzadeh Lauren S. Richardson Ananth Kumar Kammala Angela Mosebarger Mohamed Bettayeb Sungjin Kim Po Yi Lam Enkhtuya Radnaa Arum Han Ramkumar Menon |
| author_sort | Melody Safarzadeh |
| collection | DOAJ |
| description | Pregnant women and their fetuses are often excluded from clinical trials due to missing drug-related pre-clinical trial information at the human feto-maternal interface (FMi). The two interfaces-placenta/decidua and fetal membranes/decidua are gatekeepers of drug transport; however, testing their functions is impractical during pregnancy. Limitations of current in-vivo/in-vitro models have hampered drug development and testing during pregnancy. Hence, major complications like preterm births and maternal and neonatal mortalities remain high. Advancements in organ-on-chip (OOC) platforms to test drug kinetics and efficacy and novel extracellular vesicle-based fetal drug delivery are expected to accelerate preclinical trials related to pregnancy complications. Here we report the development and testing of a humanized multi-organ fetal membrane/placenta (fetal)-decidua (maternal) interface OOC (FMi-PLA-OOC) that contains seven cell types interconnected through microchannels to maintain intercellular interactions as seen in-utero. Cytotoxicity, propagation, mechanism of action, and efficacy of engineered extracellular vesicles containing anti-inflammatory interleukin (IL)-10 (eIL-10) were evaluated to reduce FMi inflammation associated with preterm birth. A healthy and disease model (lipopolysaccharide-infectious inflammation) of the FMi-PLA-OOC was created and co-treated with eIL-10. eIL-10 propagated from the maternal to fetal side within 72-h, localized in all cell types, showed no cytotoxicity, activated IL-10 signaling pathways, and reduced lipopolysaccharide-induced inflammation (minimized NF-kB activation and proinflammatory cytokine production). These data recapitulated eIL-10s’ ability to reduce inflammation and delay infection-associated preterm birth in mouse models, suggesting FMi-PLA-OOC as an alternative approach to using animal models. Additionally, we report the utility of eIL-10 that can traverse through FMis to reduce inflammation-associated pregnancy complications. |
| format | Article |
| id | doaj-art-09b6abcfbed8466d834a08a6da8f6210 |
| institution | Kabale University |
| issn | 2773-0417 |
| language | English |
| publishDate | 2024-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Extracellular Vesicle |
| spelling | doaj-art-09b6abcfbed8466d834a08a6da8f62102024-11-23T06:34:54ZengElsevierExtracellular Vesicle2773-04172024-06-013100035A multi-organ, feto-maternal interface organ-on-chip, models pregnancy pathology and is a useful preclinical extracellular vesicle drug trial platformMelody Safarzadeh0Lauren S. Richardson1Ananth Kumar Kammala2Angela Mosebarger3Mohamed Bettayeb4Sungjin Kim5Po Yi Lam6Enkhtuya Radnaa7Arum Han8Ramkumar Menon9Division of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, USA; Division of Maternal-Fetal Medicine and Perinatal Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, USADivision of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, USADivision of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, USADivision of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, USADivision of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, USADepartment of Biomedical Engineering and Electrical and Computer Engineering, Texas A&M University, College Station, TX, USADepartment of Biomedical Engineering and Electrical and Computer Engineering, Texas A&M University, College Station, TX, USADivision of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, USADepartment of Biomedical Engineering and Electrical and Computer Engineering, Texas A&M University, College Station, TX, USADivision of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, USA; Corresponding author.Pregnant women and their fetuses are often excluded from clinical trials due to missing drug-related pre-clinical trial information at the human feto-maternal interface (FMi). The two interfaces-placenta/decidua and fetal membranes/decidua are gatekeepers of drug transport; however, testing their functions is impractical during pregnancy. Limitations of current in-vivo/in-vitro models have hampered drug development and testing during pregnancy. Hence, major complications like preterm births and maternal and neonatal mortalities remain high. Advancements in organ-on-chip (OOC) platforms to test drug kinetics and efficacy and novel extracellular vesicle-based fetal drug delivery are expected to accelerate preclinical trials related to pregnancy complications. Here we report the development and testing of a humanized multi-organ fetal membrane/placenta (fetal)-decidua (maternal) interface OOC (FMi-PLA-OOC) that contains seven cell types interconnected through microchannels to maintain intercellular interactions as seen in-utero. Cytotoxicity, propagation, mechanism of action, and efficacy of engineered extracellular vesicles containing anti-inflammatory interleukin (IL)-10 (eIL-10) were evaluated to reduce FMi inflammation associated with preterm birth. A healthy and disease model (lipopolysaccharide-infectious inflammation) of the FMi-PLA-OOC was created and co-treated with eIL-10. eIL-10 propagated from the maternal to fetal side within 72-h, localized in all cell types, showed no cytotoxicity, activated IL-10 signaling pathways, and reduced lipopolysaccharide-induced inflammation (minimized NF-kB activation and proinflammatory cytokine production). These data recapitulated eIL-10s’ ability to reduce inflammation and delay infection-associated preterm birth in mouse models, suggesting FMi-PLA-OOC as an alternative approach to using animal models. Additionally, we report the utility of eIL-10 that can traverse through FMis to reduce inflammation-associated pregnancy complications.http://www.sciencedirect.com/science/article/pii/S2773041724000027Microphysiological systemsPlacentaFetal membraneInterleukin-10EVsPreterm birth |
| spellingShingle | Melody Safarzadeh Lauren S. Richardson Ananth Kumar Kammala Angela Mosebarger Mohamed Bettayeb Sungjin Kim Po Yi Lam Enkhtuya Radnaa Arum Han Ramkumar Menon A multi-organ, feto-maternal interface organ-on-chip, models pregnancy pathology and is a useful preclinical extracellular vesicle drug trial platform Extracellular Vesicle Microphysiological systems Placenta Fetal membrane Interleukin-10 EVs Preterm birth |
| title | A multi-organ, feto-maternal interface organ-on-chip, models pregnancy pathology and is a useful preclinical extracellular vesicle drug trial platform |
| title_full | A multi-organ, feto-maternal interface organ-on-chip, models pregnancy pathology and is a useful preclinical extracellular vesicle drug trial platform |
| title_fullStr | A multi-organ, feto-maternal interface organ-on-chip, models pregnancy pathology and is a useful preclinical extracellular vesicle drug trial platform |
| title_full_unstemmed | A multi-organ, feto-maternal interface organ-on-chip, models pregnancy pathology and is a useful preclinical extracellular vesicle drug trial platform |
| title_short | A multi-organ, feto-maternal interface organ-on-chip, models pregnancy pathology and is a useful preclinical extracellular vesicle drug trial platform |
| title_sort | multi organ feto maternal interface organ on chip models pregnancy pathology and is a useful preclinical extracellular vesicle drug trial platform |
| topic | Microphysiological systems Placenta Fetal membrane Interleukin-10 EVs Preterm birth |
| url | http://www.sciencedirect.com/science/article/pii/S2773041724000027 |
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