Nanoparticle-encapsulated siRNAs for gene silencing in the haematopoietic stem-cell niche
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...
Gespeichert in:
| Veröffentlicht in: | Nature biomedical engineering 2020-11, Vol.4 (11), p.1076-1089 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1089 |
|---|---|
| container_issue | 11 |
| container_start_page | 1076 |
| container_title | Nature biomedical engineering |
| container_volume | 4 |
| creator | Krohn-Grimberghe, Marvin Mitchell, Michael J. Schloss, Maximilian J. Khan, Omar F. Courties, Gabriel Guimaraes, Pedro P. G. 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 |
| description | 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
Mcp
1
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.
Systemically injected lipid–polymer nanoparticles encapsulating small interfering RNA for silencing genes in bone-marrow endothelial cells of mice improved the healing of the mice after myocardial infarction. |
| doi_str_mv | 10.1038/s41551-020-00623-7 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7655681</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2471540910</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-2c838e068b1c770deee7857c844b7b2a848337946027b0b6e48a7017171674ed3</originalsourceid><addsrcrecordid>eNp9UV1LHDEUDUWpsvoH-lAG-pz2ZpLJzb4URNQKYqG0oE8hk727G5lNxmRW8N83da3Vl5KHJJyPezmHsQ8CPguQ5ktRousEhxY4gG4lx3fssBUdcqP0zd6r9wE7LuUOAMRcqjl279mBlFWnAQ7Z7bWLaXR5Cn4gTtG7sWwHN9GiKeHH9Ulplik3K4pU_0PFQ1w1ITbTmpq1o42b0pgCVXlTJtpwT8PQxODXdMT2l24odPx8z9iv87Ofp9_41feLy9OTK-4Vqom33khDoE0vPCIsiAhNh94o1WPfOqOMlDhXGlrsodekjEMQWI9GRQs5Y193vuO239DCU5yyG-yYw8blR5tcsG-RGNZ2lR4s6q7TRlSDT88GOd1vqUz2Lm1zrDvbVqHoFMxr4jPW7lg-p1IyLV8mCLB_GrG7RmxN1j41YrGKPr7e7UXyN_9KkDtCqVBcUf43-z-2vwGYg5bs</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2471540910</pqid></control><display><type>article</type><title>Nanoparticle-encapsulated siRNAs for gene silencing in the haematopoietic stem-cell niche</title><source>MEDLINE</source><source>Springer Online Journals</source><creator>Krohn-Grimberghe, Marvin ; Mitchell, Michael J. ; Schloss, Maximilian J. ; Khan, Omar F. ; Courties, Gabriel ; Guimaraes, Pedro P. G. ; 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</creator><creatorcontrib>Krohn-Grimberghe, Marvin ; Mitchell, Michael J. ; Schloss, Maximilian J. ; Khan, Omar F. ; Courties, Gabriel ; Guimaraes, Pedro P. G. ; 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</creatorcontrib><description>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
Mcp
1
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.
Systemically injected lipid–polymer nanoparticles encapsulating small interfering RNA for silencing genes in bone-marrow endothelial cells of mice improved the healing of the mice after myocardial infarction.</description><identifier>ISSN: 2157-846X</identifier><identifier>EISSN: 2157-846X</identifier><identifier>DOI: 10.1038/s41551-020-00623-7</identifier><identifier>PMID: 33020600</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>14 ; 14/63 ; 639/925/350 ; 692/4019 ; 692/699/1541 ; 692/699/249 ; Animals ; Biomedical and Life Sciences ; Biomedical Engineering/Biotechnology ; Biomedicine ; Blood vessels ; Bone healing ; Bone marrow ; Bone Marrow Cells - drug effects ; Bone Marrow Cells - metabolism ; Cardiovascular diseases ; Cells, Cultured ; Congestive heart failure ; Coronary artery disease ; Disease Models, Animal ; Drug Delivery Systems - methods ; Encapsulation ; Endothelial cells ; Endothelial Cells - drug effects ; Endothelial Cells - metabolism ; Gene silencing ; Gene Silencing - drug effects ; Genes ; Healing ; Heart attacks ; Hematopoietic stem cells ; Hematopoietic Stem Cells - drug effects ; Hematopoietic Stem Cells - metabolism ; Leukocytes ; Lipids ; Mice, Inbred C57BL ; Monocyte chemoattractant protein 1 ; Monocytes ; Myocardial infarction ; Myocardial Infarction - prevention & control ; Nanoparticles ; Nanoparticles - administration & dosage ; Nanoparticles - chemistry ; Polymers ; Progenitor cells ; Proteins ; Ribonucleic acid ; RNA ; RNA, Small Interfering - administration & dosage ; RNA, Small Interfering - chemistry ; RNA-mediated interference ; SDF-1 protein ; siRNA ; Stem Cell Niche - genetics ; Stem cells ; Therapeutic applications</subject><ispartof>Nature biomedical engineering, 2020-11, Vol.4 (11), p.1076-1089</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-2c838e068b1c770deee7857c844b7b2a848337946027b0b6e48a7017171674ed3</citedby><cites>FETCH-LOGICAL-c474t-2c838e068b1c770deee7857c844b7b2a848337946027b0b6e48a7017171674ed3</cites><orcidid>0000-0003-3811-2369 ; 0000-0002-3148-8411 ; 0000-0003-1009-658X ; 0000-0003-4255-0492 ; 0000-0002-3628-2244 ; 0000-0001-5629-4798 ; 0000-0001-8607-0189 ; 0000-0001-5566-6692 ; 0000-0002-3163-9152 ; 0000-0001-7812-2583 ; 0000-0002-4021-1887</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41551-020-00623-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41551-020-00623-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27922,27923,41486,42555,51317</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33020600$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Krohn-Grimberghe, Marvin</creatorcontrib><creatorcontrib>Mitchell, Michael J.</creatorcontrib><creatorcontrib>Schloss, Maximilian J.</creatorcontrib><creatorcontrib>Khan, Omar F.</creatorcontrib><creatorcontrib>Courties, Gabriel</creatorcontrib><creatorcontrib>Guimaraes, Pedro P. G.</creatorcontrib><creatorcontrib>Rohde, David</creatorcontrib><creatorcontrib>Cremer, Sebastian</creatorcontrib><creatorcontrib>Kowalski, Piotr S.</creatorcontrib><creatorcontrib>Sun, Yuan</creatorcontrib><creatorcontrib>Tan, Mingchee</creatorcontrib><creatorcontrib>Webster, Jamie</creatorcontrib><creatorcontrib>Wang, Karin</creatorcontrib><creatorcontrib>Iwamoto, Yoshiko</creatorcontrib><creatorcontrib>Schmidt, Stephen P.</creatorcontrib><creatorcontrib>Wojtkiewicz, Gregory R.</creatorcontrib><creatorcontrib>Nayar, Ribhu</creatorcontrib><creatorcontrib>Frodermann, Vanessa</creatorcontrib><creatorcontrib>Hulsmans, Maarten</creatorcontrib><creatorcontrib>Chung, Amanda</creatorcontrib><creatorcontrib>Hoyer, Friedrich Felix</creatorcontrib><creatorcontrib>Swirski, Filip K.</creatorcontrib><creatorcontrib>Langer, Robert</creatorcontrib><creatorcontrib>Anderson, Daniel G.</creatorcontrib><creatorcontrib>Nahrendorf, Matthias</creatorcontrib><title>Nanoparticle-encapsulated siRNAs for gene silencing in the haematopoietic stem-cell niche</title><title>Nature biomedical engineering</title><addtitle>Nat Biomed Eng</addtitle><addtitle>Nat Biomed Eng</addtitle><description>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
Mcp
1
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.
Systemically injected lipid–polymer nanoparticles encapsulating small interfering RNA for silencing genes in bone-marrow endothelial cells of mice improved the healing of the mice after myocardial infarction.</description><subject>14</subject><subject>14/63</subject><subject>639/925/350</subject><subject>692/4019</subject><subject>692/699/1541</subject><subject>692/699/249</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering/Biotechnology</subject><subject>Biomedicine</subject><subject>Blood vessels</subject><subject>Bone healing</subject><subject>Bone marrow</subject><subject>Bone Marrow Cells - drug effects</subject><subject>Bone Marrow Cells - metabolism</subject><subject>Cardiovascular diseases</subject><subject>Cells, Cultured</subject><subject>Congestive heart failure</subject><subject>Coronary artery disease</subject><subject>Disease Models, Animal</subject><subject>Drug Delivery Systems - methods</subject><subject>Encapsulation</subject><subject>Endothelial cells</subject><subject>Endothelial Cells - drug effects</subject><subject>Endothelial Cells - metabolism</subject><subject>Gene silencing</subject><subject>Gene Silencing - drug effects</subject><subject>Genes</subject><subject>Healing</subject><subject>Heart attacks</subject><subject>Hematopoietic stem cells</subject><subject>Hematopoietic Stem Cells - drug effects</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>Leukocytes</subject><subject>Lipids</subject><subject>Mice, Inbred C57BL</subject><subject>Monocyte chemoattractant protein 1</subject><subject>Monocytes</subject><subject>Myocardial infarction</subject><subject>Myocardial Infarction - prevention & control</subject><subject>Nanoparticles</subject><subject>Nanoparticles - administration & dosage</subject><subject>Nanoparticles - chemistry</subject><subject>Polymers</subject><subject>Progenitor cells</subject><subject>Proteins</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Small Interfering - administration & dosage</subject><subject>RNA, Small Interfering - chemistry</subject><subject>RNA-mediated interference</subject><subject>SDF-1 protein</subject><subject>siRNA</subject><subject>Stem Cell Niche - genetics</subject><subject>Stem cells</subject><subject>Therapeutic applications</subject><issn>2157-846X</issn><issn>2157-846X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9UV1LHDEUDUWpsvoH-lAG-pz2ZpLJzb4URNQKYqG0oE8hk727G5lNxmRW8N83da3Vl5KHJJyPezmHsQ8CPguQ5ktRousEhxY4gG4lx3fssBUdcqP0zd6r9wE7LuUOAMRcqjl279mBlFWnAQ7Z7bWLaXR5Cn4gTtG7sWwHN9GiKeHH9Ulplik3K4pU_0PFQ1w1ITbTmpq1o42b0pgCVXlTJtpwT8PQxODXdMT2l24odPx8z9iv87Ofp9_41feLy9OTK-4Vqom33khDoE0vPCIsiAhNh94o1WPfOqOMlDhXGlrsodekjEMQWI9GRQs5Y193vuO239DCU5yyG-yYw8blR5tcsG-RGNZ2lR4s6q7TRlSDT88GOd1vqUz2Lm1zrDvbVqHoFMxr4jPW7lg-p1IyLV8mCLB_GrG7RmxN1j41YrGKPr7e7UXyN_9KkDtCqVBcUf43-z-2vwGYg5bs</recordid><startdate>20201101</startdate><enddate>20201101</enddate><creator>Krohn-Grimberghe, Marvin</creator><creator>Mitchell, Michael J.</creator><creator>Schloss, Maximilian J.</creator><creator>Khan, Omar F.</creator><creator>Courties, Gabriel</creator><creator>Guimaraes, Pedro P. G.</creator><creator>Rohde, David</creator><creator>Cremer, Sebastian</creator><creator>Kowalski, Piotr S.</creator><creator>Sun, Yuan</creator><creator>Tan, Mingchee</creator><creator>Webster, Jamie</creator><creator>Wang, Karin</creator><creator>Iwamoto, Yoshiko</creator><creator>Schmidt, Stephen P.</creator><creator>Wojtkiewicz, Gregory R.</creator><creator>Nayar, Ribhu</creator><creator>Frodermann, Vanessa</creator><creator>Hulsmans, Maarten</creator><creator>Chung, Amanda</creator><creator>Hoyer, Friedrich Felix</creator><creator>Swirski, Filip K.</creator><creator>Langer, Robert</creator><creator>Anderson, Daniel G.</creator><creator>Nahrendorf, Matthias</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>ABJCF</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>L6V</scope><scope>LK8</scope><scope>M7P</scope><scope>M7S</scope><scope>P5Z</scope><scope>P62</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-3811-2369</orcidid><orcidid>https://orcid.org/0000-0002-3148-8411</orcidid><orcidid>https://orcid.org/0000-0003-1009-658X</orcidid><orcidid>https://orcid.org/0000-0003-4255-0492</orcidid><orcidid>https://orcid.org/0000-0002-3628-2244</orcidid><orcidid>https://orcid.org/0000-0001-5629-4798</orcidid><orcidid>https://orcid.org/0000-0001-8607-0189</orcidid><orcidid>https://orcid.org/0000-0001-5566-6692</orcidid><orcidid>https://orcid.org/0000-0002-3163-9152</orcidid><orcidid>https://orcid.org/0000-0001-7812-2583</orcidid><orcidid>https://orcid.org/0000-0002-4021-1887</orcidid></search><sort><creationdate>20201101</creationdate><title>Nanoparticle-encapsulated siRNAs for gene silencing in the haematopoietic stem-cell niche</title><author>Krohn-Grimberghe, Marvin ; Mitchell, Michael J. ; Schloss, Maximilian J. ; Khan, Omar F. ; Courties, Gabriel ; Guimaraes, Pedro P. G. ; 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><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-2c838e068b1c770deee7857c844b7b2a848337946027b0b6e48a7017171674ed3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>14</topic><topic>14/63</topic><topic>639/925/350</topic><topic>692/4019</topic><topic>692/699/1541</topic><topic>692/699/249</topic><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering/Biotechnology</topic><topic>Biomedicine</topic><topic>Blood vessels</topic><topic>Bone healing</topic><topic>Bone marrow</topic><topic>Bone Marrow Cells - drug effects</topic><topic>Bone Marrow Cells - metabolism</topic><topic>Cardiovascular diseases</topic><topic>Cells, Cultured</topic><topic>Congestive heart failure</topic><topic>Coronary artery disease</topic><topic>Disease Models, Animal</topic><topic>Drug Delivery Systems - methods</topic><topic>Encapsulation</topic><topic>Endothelial cells</topic><topic>Endothelial Cells - drug effects</topic><topic>Endothelial Cells - metabolism</topic><topic>Gene silencing</topic><topic>Gene Silencing - drug effects</topic><topic>Genes</topic><topic>Healing</topic><topic>Heart attacks</topic><topic>Hematopoietic stem cells</topic><topic>Hematopoietic Stem Cells - drug effects</topic><topic>Hematopoietic Stem Cells - metabolism</topic><topic>Leukocytes</topic><topic>Lipids</topic><topic>Mice, Inbred C57BL</topic><topic>Monocyte chemoattractant protein 1</topic><topic>Monocytes</topic><topic>Myocardial infarction</topic><topic>Myocardial Infarction - prevention & control</topic><topic>Nanoparticles</topic><topic>Nanoparticles - administration & dosage</topic><topic>Nanoparticles - chemistry</topic><topic>Polymers</topic><topic>Progenitor cells</topic><topic>Proteins</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Small Interfering - administration & dosage</topic><topic>RNA, Small Interfering - chemistry</topic><topic>RNA-mediated interference</topic><topic>SDF-1 protein</topic><topic>siRNA</topic><topic>Stem Cell Niche - genetics</topic><topic>Stem cells</topic><topic>Therapeutic applications</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Krohn-Grimberghe, Marvin</creatorcontrib><creatorcontrib>Mitchell, Michael J.</creatorcontrib><creatorcontrib>Schloss, Maximilian J.</creatorcontrib><creatorcontrib>Khan, Omar F.</creatorcontrib><creatorcontrib>Courties, Gabriel</creatorcontrib><creatorcontrib>Guimaraes, Pedro P. G.</creatorcontrib><creatorcontrib>Rohde, David</creatorcontrib><creatorcontrib>Cremer, Sebastian</creatorcontrib><creatorcontrib>Kowalski, Piotr S.</creatorcontrib><creatorcontrib>Sun, Yuan</creatorcontrib><creatorcontrib>Tan, Mingchee</creatorcontrib><creatorcontrib>Webster, Jamie</creatorcontrib><creatorcontrib>Wang, Karin</creatorcontrib><creatorcontrib>Iwamoto, Yoshiko</creatorcontrib><creatorcontrib>Schmidt, Stephen P.</creatorcontrib><creatorcontrib>Wojtkiewicz, Gregory R.</creatorcontrib><creatorcontrib>Nayar, Ribhu</creatorcontrib><creatorcontrib>Frodermann, Vanessa</creatorcontrib><creatorcontrib>Hulsmans, Maarten</creatorcontrib><creatorcontrib>Chung, Amanda</creatorcontrib><creatorcontrib>Hoyer, Friedrich Felix</creatorcontrib><creatorcontrib>Swirski, Filip K.</creatorcontrib><creatorcontrib>Langer, Robert</creatorcontrib><creatorcontrib>Anderson, Daniel G.</creatorcontrib><creatorcontrib>Nahrendorf, Matthias</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Engineering Collection</collection><collection>Biological Sciences</collection><collection>Biological Science Database</collection><collection>ProQuest Engineering Database</collection><collection>ProQuest Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature biomedical engineering</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Krohn-Grimberghe, Marvin</au><au>Mitchell, Michael J.</au><au>Schloss, Maximilian J.</au><au>Khan, Omar F.</au><au>Courties, Gabriel</au><au>Guimaraes, Pedro P. G.</au><au>Rohde, David</au><au>Cremer, Sebastian</au><au>Kowalski, Piotr S.</au><au>Sun, Yuan</au><au>Tan, Mingchee</au><au>Webster, Jamie</au><au>Wang, Karin</au><au>Iwamoto, Yoshiko</au><au>Schmidt, Stephen P.</au><au>Wojtkiewicz, Gregory R.</au><au>Nayar, Ribhu</au><au>Frodermann, Vanessa</au><au>Hulsmans, Maarten</au><au>Chung, Amanda</au><au>Hoyer, Friedrich Felix</au><au>Swirski, Filip K.</au><au>Langer, Robert</au><au>Anderson, Daniel G.</au><au>Nahrendorf, Matthias</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nanoparticle-encapsulated siRNAs for gene silencing in the haematopoietic stem-cell niche</atitle><jtitle>Nature biomedical engineering</jtitle><stitle>Nat Biomed Eng</stitle><addtitle>Nat Biomed Eng</addtitle><date>2020-11-01</date><risdate>2020</risdate><volume>4</volume><issue>11</issue><spage>1076</spage><epage>1089</epage><pages>1076-1089</pages><issn>2157-846X</issn><eissn>2157-846X</eissn><abstract>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
Mcp
1
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.
Systemically injected lipid–polymer nanoparticles encapsulating small interfering RNA for silencing genes in bone-marrow endothelial cells of mice improved the healing of the mice after myocardial infarction.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>33020600</pmid><doi>10.1038/s41551-020-00623-7</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-3811-2369</orcidid><orcidid>https://orcid.org/0000-0002-3148-8411</orcidid><orcidid>https://orcid.org/0000-0003-1009-658X</orcidid><orcidid>https://orcid.org/0000-0003-4255-0492</orcidid><orcidid>https://orcid.org/0000-0002-3628-2244</orcidid><orcidid>https://orcid.org/0000-0001-5629-4798</orcidid><orcidid>https://orcid.org/0000-0001-8607-0189</orcidid><orcidid>https://orcid.org/0000-0001-5566-6692</orcidid><orcidid>https://orcid.org/0000-0002-3163-9152</orcidid><orcidid>https://orcid.org/0000-0001-7812-2583</orcidid><orcidid>https://orcid.org/0000-0002-4021-1887</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2157-846X |
| ispartof | Nature biomedical engineering, 2020-11, Vol.4 (11), p.1076-1089 |
| issn | 2157-846X 2157-846X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7655681 |
| source | MEDLINE; Springer Online Journals |
| subjects | 14 14/63 639/925/350 692/4019 692/699/1541 692/699/249 Animals Biomedical and Life Sciences Biomedical Engineering/Biotechnology Biomedicine Blood vessels Bone healing Bone marrow Bone Marrow Cells - drug effects Bone Marrow Cells - metabolism Cardiovascular diseases Cells, Cultured Congestive heart failure Coronary artery disease Disease Models, Animal Drug Delivery Systems - methods Encapsulation Endothelial cells Endothelial Cells - drug effects Endothelial Cells - metabolism Gene silencing Gene Silencing - drug effects Genes Healing Heart attacks Hematopoietic stem cells Hematopoietic Stem Cells - drug effects Hematopoietic Stem Cells - metabolism Leukocytes Lipids Mice, Inbred C57BL Monocyte chemoattractant protein 1 Monocytes Myocardial infarction Myocardial Infarction - prevention & control Nanoparticles Nanoparticles - administration & dosage Nanoparticles - chemistry Polymers Progenitor cells Proteins Ribonucleic acid RNA RNA, Small Interfering - administration & dosage RNA, Small Interfering - chemistry RNA-mediated interference SDF-1 protein siRNA Stem Cell Niche - genetics Stem cells Therapeutic applications |
| title | Nanoparticle-encapsulated siRNAs for gene silencing in the haematopoietic stem-cell niche |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-14T14%3A56%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Nanoparticle-encapsulated%20siRNAs%20for%20gene%20silencing%20in%20the%20haematopoietic%20stem-cell%20niche&rft.jtitle=Nature%20biomedical%20engineering&rft.au=Krohn-Grimberghe,%20Marvin&rft.date=2020-11-01&rft.volume=4&rft.issue=11&rft.spage=1076&rft.epage=1089&rft.pages=1076-1089&rft.issn=2157-846X&rft.eissn=2157-846X&rft_id=info:doi/10.1038/s41551-020-00623-7&rft_dat=%3Cproquest_pubme%3E2471540910%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2471540910&rft_id=info:pmid/33020600&rfr_iscdi=true |