Nanoparticle-encapsulated siRNAs for gene silencing in the haematopoietic stem-cell niche.

Autor: Krohn-Grimberghe M; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany., Mitchell MJ; Department of Chemical Engineering, David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA., Schloss MJ; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Khan OF; Department of Chemical Engineering, David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA., Courties G; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Guimaraes PPG; Department of Chemical Engineering, David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA., Rohde D; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Cremer S; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Kowalski PS; Department of Chemical Engineering, David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA., Sun Y; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Tan M; Department of Chemical Engineering, David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA., Webster J; Department of Chemical Engineering, David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA., Wang K; Molecular and Integrative Physiological Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Iwamoto Y; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Schmidt SP; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Wojtkiewicz GR; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Nayar R; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Frodermann V; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Hulsmans M; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Chung A; Molecular and Integrative Physiological Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Hoyer FF; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Swirski FK; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Langer R; Department of Chemical Engineering, David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA., Anderson DG; Department of Chemical Engineering, David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA. dgander@mit.edu., Nahrendorf M; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. mnahrendorf@mgh.harvard.edu.; Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. mnahrendorf@mgh.harvard.edu.; Department of Internal Medicine I, University Hospital Wuerzburg, Wuerzburg, Germany. mnahrendorf@mgh.harvard.edu.
Jazyk: angličtina
Zdroj: Nature biomedical engineering [Nat Biomed Eng] 2020 Nov; Vol. 4 (11), pp. 1076-1089. Date of Electronic Publication: 2020 Oct 05.
DOI: 10.1038/s41551-020-00623-7
Abstrakt: 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.
Databáze: MEDLINE