Generation of vascularized 3-dimensional (3D) kidney organoids from human pluripotent stem cells
Human pluripotent stem cell (hPSC)-derived kidney organoids are revolutionizing the way we investigate renal physiopathology and development. However, intrinsic limitations such as efficiency and a lack of control over the cell types differentiating within, hamper their full utility. Here, we presen...
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| Format: | Thesis-Doctor of Philosophy |
| Language: | English |
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Nanyang Technological University
2020
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| Online Access: | https://hdl.handle.net/10356/145522 |
| _version_ | 1824456491592056832 |
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| author | Low, Jian Hui |
| author2 | XIA Yun |
| author_facet | XIA Yun Low, Jian Hui |
| author_sort | Low, Jian Hui |
| collection | NTU |
| description | Human pluripotent stem cell (hPSC)-derived kidney organoids are revolutionizing the way we investigate renal physiopathology and development. However, intrinsic limitations such as efficiency and a lack of control over the cell types differentiating within, hamper their full utility. Here, we present the establishment of a highly efficient protocol for differentiating hPSCs into kidney organoids comprised of segmented nephrons, vasculature, and interstitial cells. By temporal modulation of canonical WNT-signalling, we could influence proximal-to- distal nephron patterning and the corresponding vasculature content. We identified a novel renal vascular progenitor that responds to podocyte-derived VEGF-A and mature into CD31+ endothelium. Following implantation into an immunocompromised host, kidney organoids rapidly engraft and undergo functional maturation as demonstrated by size-specific dextran filtration and the accumulation of putative filtrate within tubules. Our work represents an advanced version of kidney organoids that promise to offer extensive utility in both basic science and clinical practice. |
| first_indexed | 2025-02-19T03:54:57Z |
| format | Thesis-Doctor of Philosophy |
| id | ntu-10356/145522 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:54:57Z |
| publishDate | 2020 |
| publisher | Nanyang Technological University |
| record_format | dspace |
| spelling | ntu-10356/1455222023-03-05T17:10:47Z Generation of vascularized 3-dimensional (3D) kidney organoids from human pluripotent stem cells Low, Jian Hui XIA Yun Lee Kong Chian School of Medicine (LKCMedicine) yunxia@ntu.edu.sg Science::Medicine Human pluripotent stem cell (hPSC)-derived kidney organoids are revolutionizing the way we investigate renal physiopathology and development. However, intrinsic limitations such as efficiency and a lack of control over the cell types differentiating within, hamper their full utility. Here, we present the establishment of a highly efficient protocol for differentiating hPSCs into kidney organoids comprised of segmented nephrons, vasculature, and interstitial cells. By temporal modulation of canonical WNT-signalling, we could influence proximal-to- distal nephron patterning and the corresponding vasculature content. We identified a novel renal vascular progenitor that responds to podocyte-derived VEGF-A and mature into CD31+ endothelium. Following implantation into an immunocompromised host, kidney organoids rapidly engraft and undergo functional maturation as demonstrated by size-specific dextran filtration and the accumulation of putative filtrate within tubules. Our work represents an advanced version of kidney organoids that promise to offer extensive utility in both basic science and clinical practice. Doctor of Philosophy 2020-12-27T13:20:54Z 2020-12-27T13:20:54Z 2020 Thesis-Doctor of Philosophy Low, J. H. (2020). Generation of vascularized 3-dimensional (3D) kidney organoids from human pluripotent stem cells. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/145522 10.32657/10356/145522 en This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University |
| spellingShingle | Science::Medicine Low, Jian Hui Generation of vascularized 3-dimensional (3D) kidney organoids from human pluripotent stem cells |
| title | Generation of vascularized 3-dimensional (3D) kidney organoids from human pluripotent stem cells |
| title_full | Generation of vascularized 3-dimensional (3D) kidney organoids from human pluripotent stem cells |
| title_fullStr | Generation of vascularized 3-dimensional (3D) kidney organoids from human pluripotent stem cells |
| title_full_unstemmed | Generation of vascularized 3-dimensional (3D) kidney organoids from human pluripotent stem cells |
| title_short | Generation of vascularized 3-dimensional (3D) kidney organoids from human pluripotent stem cells |
| title_sort | generation of vascularized 3 dimensional 3d kidney organoids from human pluripotent stem cells |
| topic | Science::Medicine |
| url | https://hdl.handle.net/10356/145522 |
| work_keys_str_mv | AT lowjianhui generationofvascularized3dimensional3dkidneyorganoidsfromhumanpluripotentstemcells |