title: Design considerations of iron-based nanoclusters for noninvasive tracking of mesenchymal stem cell homing.
abstract: Stem-cell-based therapies have attracted considerable interest in regenerative medicine and oncological research. However, a major limitation of systemic delivery of stem cells is the low homing efficiency to the target site. Here, we report a serendipitous finding that various iron-based magnetic nanoparticles (MNPs) actively augment chemokine receptor CXCR4 expression of bone-marrow-derived mesenchymal stem cells (MSCs). On the basis of this observation, we designed an iron-based nanocluster that can effectively label MSCs, improve cell homing efficiency, and track the fate of the cells in vivo. Using this nanocluster, the labeled MSCs were accurately monitored by magnetic resonance imaging and improved the homing to both traumatic brain injury and glioblastoma models as compared to unlabeled MSCs. Our findings provide a simple and safe method for imaging and targeted delivery of stem cells and extend the potential applications of iron-based MNPs in regenerative medicine and oncology.
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland 20892, United States.
authors.forename: Xinglu
authors.initials: X
authors.lastname: Huang
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaolian
authors.initials: X
authors.lastname: Sun
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Choi
authors.forename: Dingbin
authors.initials: D
authors.lastname: Liu
authors.forename: Jin-sil
authors.initials: JS
authors.lastname: Choi
authors.forename: Tae-Hyun
authors.initials: TH
authors.lastname: Shin
authors.forename: Jinwoo
authors.initials: J
authors.lastname: Cheon
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D001665:Binding Sites; D001854:Bone Marrow Cells / Q000166:cytology; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000473:pathology*; D019070:Cell Lineage; D002462:Cell Membrane / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000378:metabolism; D002633:Chemotaxis; D005290:Ferric Compounds / Q000737:chemistry*; D005909:Glioblastoma / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D036103:Nanotechnology / Q000379:methods*; D010957:Plasmids / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D044968:Regenerative Medicine / Q000379:methods; D013234:Stem Cells / Q000166:cytology
chemical_list: C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D005290:Ferric Compounds; D019718:Receptors, CXCR4; C000499:ferric oxide
references.citation: Mol Ther. 2008 Mar;16(3):571-9
references.pmid: 18253156
references.citation: Nature. 2002 Jul 4;418(6893):41-9
references.pmid: 12077603
references.citation: PLoS One. 2013 May 09;8(5):e62703
references.pmid: 23671625
references.citation: Magn Reson Imaging. 2008 Sep;26(7):994-8
references.pmid: 18479873
references.citation: Science. 1999 Feb 5;283(5403):845-8
references.pmid: 9933168
references.citation: Circulation. 2003 Aug 19;108(7):863-8
references.pmid: 12900340
references.citation: Biometals. 2012 Aug;25(4):749-59
references.pmid: 22476617
references.citation: Biomaterials. 2012 Sep;33(26):6186-93
references.pmid: 22687759
references.citation: Cell Stem Cell. 2008 Mar 6;2(3):205-13
references.pmid: 18371446
references.citation: J Stem Cells. 2012;7(2):87-95
references.pmid: 23550347
references.citation: Cancer Res. 2009 Dec 1;69(23):8862-7
references.pmid: 19920196
references.citation: NMR Biomed. 2010 Jun;23(5):514-22
references.pmid: 20175151
references.citation: Nat Med. 2004 Aug;10(8):858-64
references.pmid: 15235597
references.citation: J Am Chem Soc. 2004 Jan 14;126(1):273-9
references.pmid: 14709092
references.citation: Stem Cells. 2006 Apr;24(4):1020-9
references.pmid: 16339642
references.citation: Blood. 2006 Dec 1;108(12):3938-44
references.pmid: 16896152
references.citation: Stem Cells. 2009 Jul;27(7):1548-58
references.pmid: 19544460
references.citation: FASEB J. 2007 Oct;21(12):3197-207
references.pmid: 17496162
references.citation: Biochemistry. 2012 Jul 24;51(29):5705-24
references.pmid: 22703180
references.citation: Clin Rev Allergy Immunol. 2013 Oct;45(2):180-92
references.pmid: 23296948
references.citation: Nat Rev Cancer. 2004 Jul;4(7):528-39
references.pmid: 15229478
references.citation: Dev Biol. 1999 Sep 15;213(2):442-56
references.pmid: 10479460
references.citation: Cell Immunol. 2013 Jan;281(1):68-75
references.pmid: 23474530
references.citation: Angew Chem Int Ed Engl. 2009;48(7):1234-8
references.pmid: 19137514
references.citation: Stem Cells. 2007 Jul;25(7):1737-45
references.pmid: 17395768
references.citation: Biomaterials. 2012 Jul;33(21):5414-22
references.pmid: 22560667
references.citation: Circulation. 2012 Jul 17;126(3):314-24
references.pmid: 22685115
references.citation: J Mol Cell Cardiol. 2008 Feb;44(2):281-92
references.pmid: 18201717
references.citation: Nature. 2003 Sep 18;425(6955):307-11
references.pmid: 13679920
references.citation: ACS Nano. 2011 Dec 27;5(12):9807-16
references.pmid: 22053840
references.citation: Stem Cells. 2007 Nov;25(11):2896-902
references.pmid: 17901396
references.citation: Neurosci Lett. 2007 Oct 16;426(2):69-74
references.pmid: 17884290
references.citation: Biomaterials. 2010 Jan;31(1):106-14
references.pmid: 19783037
references.citation: Blood. 2003 Aug 1;102(3):867-72
references.pmid: 12676779
references.citation: Blood. 2011 Dec 15;118(25):e184-91
references.pmid: 22034631
references.citation: Biomaterials. 2014 Jan;35(2):856-65
references.pmid: 24344357
references.citation: Biomaterials. 2013 Feb;34(7):1772-80
references.pmid: 23228423
references.citation: Small. 2011 Oct 4;7(19):2742-9
references.pmid: 21861295
references.citation: Cell Stem Cell. 2009 Mar 6;4(3):206-16
references.pmid: 19265660
references.citation: Angew Chem Int Ed Engl. 2012 Feb 13;51(7):1625-30
references.pmid: 22213412
references.citation: Blood. 2012 Jun 14;119(24):5782-94
references.pmid: 22394600
references.citation: N Engl J Med. 2012 Jan 26;366(4):348-59
references.pmid: 22276824
references.citation: J Am Chem Soc. 2004 Jul 14;126(27):8394-5
references.pmid: 15237993
references.citation: Neurotherapeutics. 2010 Jan;7(1):22-30
references.pmid: 20129494
references.citation: Nat Mater. 2012 Dec;11(12):1038-43
references.pmid: 23042417
references.citation: Nat Rev Clin Oncol. 2011 Sep 27;8(11):677-88
references.pmid: 21946842