title: Labeling human embryonic stem-cell-derived cardiomyocytes for tracking with MR imaging.
abstract: BACKGROUND
  Human embryonic stem cells (hESC) can generate cardiomyocytes (CM), which offer promising treatments for cardiomyopathies in children. However, challenges for clinical translation result from loss of transplanted cell from target sites and high cell death. An imaging technique that noninvasively and repetitively monitors transplanted hESC-CM could guide improvements in transplantation techniques and advance therapies.
  
  
  OBJECTIVE
  To develop a clinically applicable labeling technique for hESC-CM with FDA-approved superparamagnetic iron oxide nanoparticles (SPIO) by examining labeling before and after CM differentiation.
  
  
  METHODS
  Triplicates of hESC were labeled by simple incubation with 50 μg/ml of ferumoxides before or after differentiation into CM, then imaged on a 7T MR scanner using a T2-weighted multi-echo spin-echo sequence. Viability, iron uptake and T2-relaxation times were compared between groups using t-tests.
  
  
  RESULTS
  hESC-CM labeled before differentiation demonstrated significant MR effects, iron uptake and preserved function. hESC-CM labeled after differentiation showed no significant iron uptake or change in MR signal (P < 0.05). Morphology, differentiation and viability were consistent between experimental groups.
  
  
  CONCLUSIONS
  hESC-CM should be labeled prior to CM differentiation to achieve a significant MR signal. This technique permits monitoring delivery and engraftment of hESC-CM for potential advancements of stem cell-based therapies in the reconstitution of damaged myocardium.
authors: Pediatric Radiology, Lucile Packard Children's Hospital, Stanford School of Medicine, Stanford, CA 94305-5654, USA. rcastan@stanford.edu
authors: Rosalinda T
authors: RT
authors: Castaneda
authors: Sophie
authors: S
authors: Boddington
authors: Tobias D
authors: TD
authors: Henning
authors: Mike
authors: M
authors: Wendland
authors: Lydia
authors: L
authors: Mandrussow
authors: Siyuan
authors: S
authors: Liu
authors: Heike
authors: H
authors: Daldrup-Link
references: Invest Radiol. 1995 Oct;30(10):604-10
references: 8557500
references: Science. 1998 Nov 6;282(5391):1145-7
references: 9804556
references: Circulation. 2008 Mar 25;117(12):1555-62
references: 18332264
references: Contrast Media Mol Imaging. 2009 Jul-Aug;4(4):165-73
references: 19670250
references: Circ Res. 1994 Aug;75(2):233-44
references: 8033337
references: J Nanosci Nanotechnol. 2009 Oct;9(10):5726-30
references: 19908444
references: Exp Cell Res. 2006 Oct 15;312(17):3205-14
references: 16934250
references: Biotechnol Prog. 2009 Jan-Feb;25(1):43-51
references: 19198003
references: PLoS One. 2009 Sep 29;4(9):e7218
references: 19787043
references: NMR Biomed. 2010 Jun;23(5):514-22
references: 20175151
references: Blood. 2004 Nov 15;104(10):3410-2; author reply 3412-3
references: 15525839
references: Stem Cells. 2006 Aug;24(8):1968-75
references: 16627684
references: Cell Transplant. 2010;19(1):55-65
references: 20370988
references: Stem Cells. 2008 Feb;26(2):517-24
references: 18055451
references: Nat Rev Cardiol. 2010 Feb;7(2):97-105
references: 20027188
references: J Am Coll Cardiol. 2009 Oct 20;54(17):1619-26
references: 19833262
references: Eur Radiol. 2001;11(11):2319-31
references: 11702180
references: Magn Reson Med. 2011 Feb;65(2):564-74
references: 20928883
references: J Transl Med. 2008 Sep 30;6:54
references: 18823569
references: Cell Transplant. 2010;19(8):919-36
references: 20350351
references: Cell Transplant. 2007;16(8):849-57
references: 18088004
references: Stem Cell Res. 2009 May;2(3):198-210
references: 19393593
references: Zhonghua Yi Xue Za Zhi. 2007 Jun 19;87(23):1646-8
references: 17803860
references: Stem Cell Rev Rep. 2010 Sep;6(3):411-24
references: 20300888
references: Circulation. 2006 Feb 21;113(7):1005-14
references: 16476845
references: Life Sci. 2006 Aug 1;79(10):999-1006
references: 16828117
references: Circulation. 2003 May 13;107(18):2290-3
references: 12732608
references: Blood. 2004 Aug 15;104(4):1217-23
references: 15100158
references: J Thorac Cardiovasc Surg. 2009 May;137(5):1225-33.e1
references: 19379996
references: Invest Radiol. 2010 Oct;45(10):634-40
references: 20808236
references: Magn Reson Imaging. 1995;13(5):661-74
references: 8569441
references: Circ Res. 2008 May 9;102(9):1008-10
references: 18436793
references: Nanomedicine (Lond). 2009 Apr;4(3):305-15
references: 19331538
references: Eur Radiol. 2004 Oct;14(10):1851-8
references: 15249981
references: PLoS One. 2008;3(10):e3474
references: 18941512
references: Curr Pharm Des. 2008;14(36):3835-53
references: 19128236
references: Radiology. 2009 Mar;250(3):821-9
references: 19244049
references: Magn Reson Med. 2003 Aug;50(2):275-82
references: 12876703
references: Adv Exp Med Biol. 2006;585:19-30
references: 17120774
references: Stem Cells. 2008 Apr;26(4):864-73
references: 18218820
references: Cell Death Differ. 2007 Jul;14(7):1336-42
references: 17396130
references: Stem Cells. 2008 Oct;26(10):2644-53
references: 18669912
references: Curr Protoc Stem Cell Biol. 2009 Aug;Chapter 5:Unit 5A.3
references: 19653198
references: Magn Reson Med. 1993 Jan;29(1):32-7
references: 7678318
references: Rev Physiol Biochem Pharmacol. 2006;157:1-30
references: 17236648
references: J Vis Exp. 2008 Mar 31;(13):
references: 19066574
references: Zhonghua Xin Xue Guan Bing Za Zhi. 2007 Apr;35(4):344-9
references: 17711662
references: JACC Cardiovasc Imaging. 2009 Sep;2(9):1114-22
references: 19761992
references: Nat Clin Pract Cardiovasc Med. 2006 Mar;3 Suppl 1:S14-7
references: 16501623
references: Biochem Biophys Res Commun. 2009 Feb 20;379(4):898-903
references: 19135029
references: N Engl J Med. 2003 Apr 24;348(17):1647-55
references: 12711739
references: PLoS One. 2009 Aug 21;4(8):e6712
references: 19696933
references: Cell Transplant. 2009;18(3):297-304
references: 19558778
references: Eur Radiol. 2008 Mar;18(3):548-69
references: 17922278
references: AJR Am J Roentgenol. 2009 Aug;193(2):314-25
references: 19620426
references: Circulation. 2007 Sep 11;116(11 Suppl):I38-45
references: 17846324
references: Nat Biotechnol. 2007 Sep;25(9):1015-24
references: 17721512
references: Magn Reson Med. 2008 Jul;60(1):73-81
references: 18581415
references: Bioconjug Chem. 1999 Mar-Apr;10(2):186-91
references: 10077466
references: Circulation. 2007 Feb 6;115(5):e69-171
references: 17194875
references: Stem Cells. 2002;20(2):146-54
references: 11897871
references: Cell Transplant. 2010;19(4):431-41
references: 20149297
references: J Neurosci Res. 2004 Apr 15;76(2):232-43
references: 15048921
references: Circ Cardiovasc Imaging. 2008 Jul;1(1):6-13
references: 19808509