Nanoparticle-encapsulated siRNAs for gene silencing in the haematopoietic stem-cell niche
© 2020, The Author(s), under exclusive licence to Springer Nature Limited. Bone-marrow endothelial cells in the haematopoietic stem-cell niche form a network of blood vessels that regulates blood-cell traffic as well as the maintenance and function of haematopoietic stem and progenitor cells. Here,...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2021
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| Online Access: | https://hdl.handle.net/1721.1/133553 |
| _version_ | 1826203438312062976 |
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| author | Krohn-Grimberghe, Marvin Mitchell, Michael J Schloss, Maximilian J Khan, Omar F Courties, Gabriel Guimaraes, Pedro PG Rohde, David Cremer, Sebastian Kowalski, Piotr S Sun, Yuan Tan, Mingchee Webster, Jamie Wang, Karin Iwamoto, Yoshiko Schmidt, Stephen P Wojtkiewicz, Gregory R Nayar, Ribhu Frodermann, Vanessa Hulsmans, Maarten Chung, Amanda Hoyer, Friedrich Felix Swirski, Filip K Langer, Robert Anderson, Daniel G Nahrendorf, Matthias |
| author_facet | Krohn-Grimberghe, Marvin Mitchell, Michael J Schloss, Maximilian J Khan, Omar F Courties, Gabriel Guimaraes, Pedro PG Rohde, David Cremer, Sebastian Kowalski, Piotr S Sun, Yuan Tan, Mingchee Webster, Jamie Wang, Karin Iwamoto, Yoshiko Schmidt, Stephen P Wojtkiewicz, Gregory R Nayar, Ribhu Frodermann, Vanessa Hulsmans, Maarten Chung, Amanda Hoyer, Friedrich Felix Swirski, Filip K Langer, Robert Anderson, Daniel G Nahrendorf, Matthias |
| author_sort | Krohn-Grimberghe, Marvin |
| collection | MIT |
| description | © 2020, The Author(s), under exclusive licence to Springer Nature Limited. Bone-marrow endothelial cells in the haematopoietic stem-cell niche form a network of blood vessels that regulates blood-cell traffic as well as the maintenance and function of haematopoietic stem and progenitor cells. Here, we report the design and in vivo performance of systemically injected lipid–polymer nanoparticles encapsulating small interfering RNA (siRNA), for the silencing of genes in bone-marrow endothelial cells. In mice, nanoparticles encapsulating siRNA sequences targeting the proteins stromal-derived factor 1 (Sdf1) or monocyte chemotactic protein 1 (Mcp1) enhanced (when silencing Sdf1) or inhibited (when silencing Mcp1) the release of stem and progenitor cells and of leukocytes from the bone marrow. In a mouse model of myocardial infarction, nanoparticle-mediated inhibition of cell release from the haematopoietic niche via Mcp1 silencing reduced leukocytes in the diseased heart, improved healing after infarction and attenuated heart failure. Nanoparticle-mediated RNA interference in the haematopoietic niche could be used to investigate haematopoietic processes for therapeutic applications in cancer, infection and cardiovascular disease. |
| first_indexed | 2024-09-23T12:36:39Z |
| format | Article |
| id | mit-1721.1/133553 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T12:36:39Z |
| publishDate | 2021 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1335532021-10-28T04:02:51Z Nanoparticle-encapsulated siRNAs for gene silencing in the haematopoietic stem-cell niche Krohn-Grimberghe, Marvin Mitchell, Michael J Schloss, Maximilian J Khan, Omar F Courties, Gabriel Guimaraes, Pedro PG Rohde, David Cremer, Sebastian Kowalski, Piotr S Sun, Yuan Tan, Mingchee Webster, Jamie Wang, Karin Iwamoto, Yoshiko Schmidt, Stephen P Wojtkiewicz, Gregory R Nayar, Ribhu Frodermann, Vanessa Hulsmans, Maarten Chung, Amanda Hoyer, Friedrich Felix Swirski, Filip K Langer, Robert Anderson, Daniel G Nahrendorf, Matthias © 2020, The Author(s), under exclusive licence to Springer Nature Limited. Bone-marrow endothelial cells in the haematopoietic stem-cell niche form a network of blood vessels that regulates blood-cell traffic as well as the maintenance and function of haematopoietic stem and progenitor cells. Here, we report the design and in vivo performance of systemically injected lipid–polymer nanoparticles encapsulating small interfering RNA (siRNA), for the silencing of genes in bone-marrow endothelial cells. In mice, nanoparticles encapsulating siRNA sequences targeting the proteins stromal-derived factor 1 (Sdf1) or monocyte chemotactic protein 1 (Mcp1) enhanced (when silencing Sdf1) or inhibited (when silencing Mcp1) the release of stem and progenitor cells and of leukocytes from the bone marrow. In a mouse model of myocardial infarction, nanoparticle-mediated inhibition of cell release from the haematopoietic niche via Mcp1 silencing reduced leukocytes in the diseased heart, improved healing after infarction and attenuated heart failure. Nanoparticle-mediated RNA interference in the haematopoietic niche could be used to investigate haematopoietic processes for therapeutic applications in cancer, infection and cardiovascular disease. 2021-10-27T19:53:30Z 2021-10-27T19:53:30Z 2020 2021-06-03T17:45:58Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133553 en 10.1038/S41551-020-00623-7 Nature Biomedical Engineering Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Springer Science and Business Media LLC PMC |
| spellingShingle | Krohn-Grimberghe, Marvin Mitchell, Michael J Schloss, Maximilian J Khan, Omar F Courties, Gabriel Guimaraes, Pedro PG Rohde, David Cremer, Sebastian Kowalski, Piotr S Sun, Yuan Tan, Mingchee Webster, Jamie Wang, Karin Iwamoto, Yoshiko Schmidt, Stephen P Wojtkiewicz, Gregory R Nayar, Ribhu Frodermann, Vanessa Hulsmans, Maarten Chung, Amanda Hoyer, Friedrich Felix Swirski, Filip K Langer, Robert Anderson, Daniel G Nahrendorf, Matthias Nanoparticle-encapsulated siRNAs for gene silencing in the haematopoietic stem-cell niche |
| title | Nanoparticle-encapsulated siRNAs for gene silencing in the haematopoietic stem-cell niche |
| title_full | Nanoparticle-encapsulated siRNAs for gene silencing in the haematopoietic stem-cell niche |
| title_fullStr | Nanoparticle-encapsulated siRNAs for gene silencing in the haematopoietic stem-cell niche |
| title_full_unstemmed | Nanoparticle-encapsulated siRNAs for gene silencing in the haematopoietic stem-cell niche |
| title_short | Nanoparticle-encapsulated siRNAs for gene silencing in the haematopoietic stem-cell niche |
| title_sort | nanoparticle encapsulated sirnas for gene silencing in the haematopoietic stem cell niche |
| url | https://hdl.handle.net/1721.1/133553 |
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