The endothelium, a key actor in organ development and hPSC-derived organoid vascularization
Abstract Over the last 4 decades, cell culture techniques have evolved towards the creation of in vitro multicellular entities that incorporate the three-dimensional complexity of in vivo tissues and organs. As a result, stem cells and adult progenitor cells have been used to derive self-organized 3...
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| Format: | Article |
| Language: | English |
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BMC
2020-05-01
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| Series: | Journal of Biomedical Science |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12929-020-00661-y |
| _version_ | 1819019938928525312 |
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| author | Alejandra Vargas-Valderrama Antonietta Messina Maria Teresa Mitjavila-Garcia Hind Guenou |
| author_facet | Alejandra Vargas-Valderrama Antonietta Messina Maria Teresa Mitjavila-Garcia Hind Guenou |
| author_sort | Alejandra Vargas-Valderrama |
| collection | DOAJ |
| description | Abstract Over the last 4 decades, cell culture techniques have evolved towards the creation of in vitro multicellular entities that incorporate the three-dimensional complexity of in vivo tissues and organs. As a result, stem cells and adult progenitor cells have been used to derive self-organized 3D cell aggregates that mimic the morphological and functional traits of organs in vitro. These so-called organoids were first generated from primary animal and human tissues, then human pluripotent stem cells (hPSCs) arose as a new tool for organoid generation. Due to their self-renewal capacity and differentiation potential, hPSCs are an unlimited source of cells used for organoids. Today, hPSC-derived small intestinal, kidney, brain, liver, and pancreas organoids, among others, have been produced and are promising in vitro human models for diverse applications, including fundamental research, drug development and regenerative medicine. However, achieving in vivo-like organ complexity and maturation in vitro remains a challenge. Current hPSC-derived organoids are often limited in size and developmental state, resembling embryonic or fetal organs rather than adult organs. The use of endothelial cells to vascularize hPSC-derived organoids may represent a key to ensuring oxygen and nutrient distribution in large organoids, thus contributing to the maturation of adult-like organoids through paracrine signaling. Here, we review the current state of the art regarding vascularized hPSC-derived organoids (vhPSC-Orgs). We analyze the progress achieved in the generation of organoids derived from the three primary germ layers (endoderm, mesoderm and ectoderm) exemplified by the pancreas, liver, kidneys and brain. Special attention will be given to the role of the endothelium in the organogenesis of the aforementioned organs, the sources of endothelial cells employed in vhPSC-Org protocols and the remaining challenges preventing the creation of ex vivo functional and vascularized organs. |
| first_indexed | 2024-12-21T03:43:16Z |
| format | Article |
| id | doaj.art-ca07a3d19ef94c2ba9f61bf9ccc4f738 |
| institution | Directory Open Access Journal |
| issn | 1423-0127 |
| language | English |
| last_indexed | 2024-12-21T03:43:16Z |
| publishDate | 2020-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj.art-ca07a3d19ef94c2ba9f61bf9ccc4f7382022-12-21T19:17:10ZengBMCJournal of Biomedical Science1423-01272020-05-0127111310.1186/s12929-020-00661-yThe endothelium, a key actor in organ development and hPSC-derived organoid vascularizationAlejandra Vargas-Valderrama0Antonietta Messina1Maria Teresa Mitjavila-Garcia2Hind Guenou3INSERM UMRS-MD 1197, Université Paris Sud-Université Paris-Saclay. Hôpital Paul BrousseDHU HépatinovINSERM UMRS-MD 1197, Université Paris Sud-Université Paris-Saclay. Hôpital Paul BrousseINSERM UMRS-MD 1197, Université Paris Sud-Université Paris-Saclay. Hôpital Paul BrousseAbstract Over the last 4 decades, cell culture techniques have evolved towards the creation of in vitro multicellular entities that incorporate the three-dimensional complexity of in vivo tissues and organs. As a result, stem cells and adult progenitor cells have been used to derive self-organized 3D cell aggregates that mimic the morphological and functional traits of organs in vitro. These so-called organoids were first generated from primary animal and human tissues, then human pluripotent stem cells (hPSCs) arose as a new tool for organoid generation. Due to their self-renewal capacity and differentiation potential, hPSCs are an unlimited source of cells used for organoids. Today, hPSC-derived small intestinal, kidney, brain, liver, and pancreas organoids, among others, have been produced and are promising in vitro human models for diverse applications, including fundamental research, drug development and regenerative medicine. However, achieving in vivo-like organ complexity and maturation in vitro remains a challenge. Current hPSC-derived organoids are often limited in size and developmental state, resembling embryonic or fetal organs rather than adult organs. The use of endothelial cells to vascularize hPSC-derived organoids may represent a key to ensuring oxygen and nutrient distribution in large organoids, thus contributing to the maturation of adult-like organoids through paracrine signaling. Here, we review the current state of the art regarding vascularized hPSC-derived organoids (vhPSC-Orgs). We analyze the progress achieved in the generation of organoids derived from the three primary germ layers (endoderm, mesoderm and ectoderm) exemplified by the pancreas, liver, kidneys and brain. Special attention will be given to the role of the endothelium in the organogenesis of the aforementioned organs, the sources of endothelial cells employed in vhPSC-Org protocols and the remaining challenges preventing the creation of ex vivo functional and vascularized organs.http://link.springer.com/article/10.1186/s12929-020-00661-yEndothelial cellsVascularized organoidshPSCsLiverKidneyBrain |
| spellingShingle | Alejandra Vargas-Valderrama Antonietta Messina Maria Teresa Mitjavila-Garcia Hind Guenou The endothelium, a key actor in organ development and hPSC-derived organoid vascularization Journal of Biomedical Science Endothelial cells Vascularized organoids hPSCs Liver Kidney Brain |
| title | The endothelium, a key actor in organ development and hPSC-derived organoid vascularization |
| title_full | The endothelium, a key actor in organ development and hPSC-derived organoid vascularization |
| title_fullStr | The endothelium, a key actor in organ development and hPSC-derived organoid vascularization |
| title_full_unstemmed | The endothelium, a key actor in organ development and hPSC-derived organoid vascularization |
| title_short | The endothelium, a key actor in organ development and hPSC-derived organoid vascularization |
| title_sort | endothelium a key actor in organ development and hpsc derived organoid vascularization |
| topic | Endothelial cells Vascularized organoids hPSCs Liver Kidney Brain |
| url | http://link.springer.com/article/10.1186/s12929-020-00661-y |
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