Abstract
Purpose
This study investigates the effects of 111In-oxine incorporation on human mesenchymal stem cells’ (hMSC) biology and viability, and the applicability of 111In-oxine for single-photon emission computed tomography/X-ray computed tomography (SPECT/CT) monitoring of hMSC in vivo.
Procedures
HMSC were labelled with 10 Bq/cell. Cellular retention of radioactivity, cell survival, and migration were evaluated over 48 h. Metabolic activity was assessed over 14 days and the hMSC’s stem cell character was evaluated. Serial SPECT/CT was performed after intra-osseous injection to athymic rats over 48 h.
Results
Labelling efficiency was 25%, with 61% of incorporated 111In remaining in the hMSC at 48 h. The radiolabelling was without effect on cell viability, stem cell character, and plasticity, whereas metabolic activity and migration were significantly reduced. Grafted cells could be imaged in situ with SPECT/CT.
Conclusions
111In-oxine labelling moderately impaired hMSC’s functional integrity while preserving their stem cell character. Combined SPECT/CT imaging of 111In-oxine-labelled hMSC opens the possibility for non-invasive sequential monitoring of therapeutic stem cells.
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References
Drosse I, Volkmer E, Capanna R et al (2008) Tissue engineering for bone defect healing: an update on a multi-component approach. Injury 39(Suppl 2):S9–S20
Zimmermann WH, Melnychenko I, Wasmeier G et al (2006) Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts. Nat Med 12:452–458
Petite H, Viateau V, Bensaid W et al (2000) Tissue-engineered bone regeneration. Nat Biotechnol 18:959–963
Wang C, Wang Z, Li A et al (2009) Repair of segmental bone-defect of goat’s tibia using a dynamic perfusion culture tissue engineering bone. J Biomed Mater Res A 92A:1145–1153
Zhou XZ, Leung VY, Dong QR et al (2008) Mesenchymal stem cell-based repair of articular cartilage with polyglycolic acid-hydroxyapatite biphasic scaffold. Int J Artif Organs 31:480–489
Badorff C, Brandes RP, Popp R et al (2003) Transdifferentiation of blood-derived human adult endothelial progenitor cells into functionally active cardiomyocytes. Circulation 107:1024–1032
Kassem M (2006) Stem cells: potential therapy for age-related diseases. Ann NY Acad Sci 1067:436–442
Liechty KW, MacKenzie TC, Shaaban AF et al (2000) Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med 6:1282–1286
Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147
Bruder SP, Jaiswal N, Ricalton NS et al (1998) Mesenchymal stem cells in osteobiology and applied bone regeneration. Clin Orthop Relat Res 355:S247–S256
Schantz JT, Hutmacher DW, Lam CX et al (2003) Repair of calvarial defects with customised tissue-engineered bone grafts II. Evaluation of cellular efficiency and efficacy in vivo. Tissue Eng 9(Suppl 1):S127–S139
Xian CJ, Foster BK (2006) Repair of injured articular and growth plate cartilage using mesenchymal stem cells and chondrogenic gene therapy. Curr Stem Cell Res Ther 1:213–229
Saldanha KJ, Piper SL, Ainslie KM, Kim HT, Majumdar S (2008) Magnetic resonance imaging of iron oxide labelled stem cells: applications to tissue engineering based regeneration of the intervertebral disc. Eur Cell Mater 16:17–25
Puppi J, Modo M (2009) Use of magnetic resonance imaging contrast agents to detect transplanted liver cells. Top Magn Reson Imaging 20:113–120
Choi HO, Hwang KJ (1987) Mechanism of ionophoric transport of indium-111 cations through a lipid bilayer membrane. J Nucl Med 28:91–96
Bindslev L, Haack-Sorensen M, Bisgaard K et al (2006) Labelling of human mesenchymal stem cells with indium-111 for SPECT imaging: effect on cell proliferation and differentiation. Eur J Nucl Med Mol Imaging 33:1171–1177
Nowak B, Weber C, Schober A et al (2007) Indium-111 oxine labelling affects the cellular integrity of haematopoietic progenitor cells. Eur J Nucl Med Mol Imaging 34:715–721
Brenner W, Aicher A, Eckey T et al (2004) 111In-labeled CD34+ hematopoietic progenitor cells in a rat myocardial infarction model. J Nucl Med 45:512–518
Acton PD, Zhou R (2005) Imaging reporter genes for cell tracking with PET and SPECT. Q J Nucl Med Mol Imaging 49:349–360
Böcker W, Yin Z, Drosse I et al (2008) Introducing a single-cell-derived human mesenchymal stem cell line expressing hTERT after lentiviral gene transfer. J Cell Mol Med 12:1347–1359
Volkmer E, Drosse I, Otto S et al (2008) Hypoxia in static and dynamic 3D culture systems for tissue engineering of bone. Tissue Eng A 14:1331–1340
Gholamrezanezhad A, Mirpour S, Ardekani JM et al (2009) Cytotoxicity of 111In-oxine on mesenchymal stem cells: a time-dependent adverse effect. Nucl Med Commun 30:210–216
Jin Y, Kong H, Stodilka RZ et al (2005) Determining the minimum number of detectable cardiac-transplanted 111In-tropolone-labelled bone-marrow-derived mesenchymal stem cells by SPECT. Phys Med Biol 50:4445–4455
Bustamante J, Dock L, Vahter M, Fowler B, Orrenius S (1997) The semiconductor elements arsenic and indium induce apoptosis in rat thymocytes. Toxicology 118:129–136
Fjälling M, Andersson P, Forssell-Aronsson E et al (1996) Systemic radionuclide therapy using indium-111-DTPA-D-Phe1-octreotide in midgut carcinoid syndrome. J Nucl Med 37:1519–1521
Martin RF, Bradley TR, Hodgson GS (1979) Cytotoxicity of an 125I-labeled DNA-binding compound that induces double-stranded DNA breaks. Cancer Res 39:3244–3247
Weaver AS, Su YP, Begun DL et al (2010) The effects of axial displacement on fracture callus morphology and MSC homing depend on the timing of application. Bone 47:41–48
Mahmood A, Lu D, Wang L et al (2001) Treatment of traumatic brain injury in female rats with intravenous administration of bone marrow stromal cells. Neurosurgery 49:1196–1203
Orlic D, Kajstura J, Chimenti S et al (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410:701–705
Assis AC, Carvalho JL, Jacoby BA et al (2010) Time-dependent migration of systemically delivered bone marrow mesenchymal stem cells to the infarcted heart. Cell Transplant 19:219–230
Haasters F, Prall WC, Anz D et al (2009) Morphological and immunocytochemical characteristics indicate the yield of early progenitors and represent a quality control for human mesenchymal stem cell culturing. J Anat 214:759–767
Schieker M, Pautke C, Haasters F et al (2007) Human mesenchymal stem cells at the single-cell level: simultaneous seven-colour immunofluorescence. J Anat 210:592–599
Jaiswal RK, Jaiswal N, Bruder SP et al (2000) Adult human mesenchymal stem cell differentiation to the osteogenic or adipogenic lineage is regulated by mitogen-activated protein kinase. J Biol Chem 275:9645–9652
Raimondo S, Penna C, Pagliaro P, Geuna S (2006) Morphological characterization of GFP stably transfected adult mesenchymal bone marrow stem cells. J Anat 208:3–12
Massoud TF, Gambhir SS (2003) Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev 17:545–580
Agriantonis DJ, Hall L, Wilson MA (2009) Utility of SPECT/CT as an adjunct to planar whole body I-131 imaging: liver metastasis from papillary thyroid cancer. Clin Nucl Med 34:247–248
Keidar Z, Israel O, Krausz Y (2003) SPECT/CT in tumor imaging: technical aspects and clinical applications. Semin Nucl Med 33:205–218
ten Berge RJ, Natarajan AT, Hardeman MR, van Royen EA, Schellekens PT (1983) Labeling with indium-111 has detrimental effects on human lymphocytes: concise communication. J Nucl Med 24:615–620
Kraitchman DL, Tatsumi M, Gilson WD et al (2005) Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction. Circulation 112:1451–1461
Shake JG, Gruber PJ, Baumgartner WA et al (2002) Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects. Ann Thorac Surg 73:1919–1925
Terrovitis JV, Bulte JW, Sarvananthan S et al (2006) Magnetic resonance imaging of ferumoxide-labeled mesenchymal stem cells seeded on collagen scaffolds-relevance to tissue engineering. Tissue Eng 12:2765–2775
Liang SX, Tan TY, Gaudry L, Chong B (2010) Differentiation and migration of Sca1+/CD31- cardiac side population cells in a murine myocardial ischemic model. Int J Cardiol 138:40–49
Lien CY, Chih-Yuan HK, Lee OK, Blunn GW, Su Y (2009) Restoration of bone mass and strength in glucocorticoid-treated mice by systemic transplantation of CXCR4 and cbfa-1 co-expressing mesenchymal stem cells. J Bone Miner Res 24:837–848
Lan X, Yin X, Wang R, Liu Y, Zhang Y (2009) Comparative study of cellular kinetics of reporter probe [(131)I]FIAU in neonatal cardiac myocytes after transfer of HSV1-tk reporter gene with two vectors. Nucl Med Biol 36:207–213
Roelants V, Labar D, de Meester C et al (2008) Comparison between adenoviral and retroviral vectors for the transduction of the thymidine kinase PET reporter gene in rat mesenchymal stem cells. J Nucl Med 49:1836–1844
Acknowledgements
This work was supported by a research grant from the Bavarian Research Foundation (Bavarian Research Collaboration for Cell-Based Regeneration of the Musculo-Skeletal System in Old Age, www.forzebra.de). We thank Mr. S. Nowak, Ms. M. Buchwald, Ms. T. Bockhöfer, and Ms. A. Brunegraf for assistance in SPECT/CT image acquisition.
Conflicts of Interest
The authors declare that they have no conflict of interest.
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Franz Josef Gildehaus and Florian Haasters contributed equally to this work
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Gildehaus, F.J., Haasters, F., Drosse, I. et al. Impact of Indium-111 Oxine Labelling on Viability of Human Mesenchymal Stem Cells In Vitro, and 3D Cell-Tracking Using SPECT/CT In Vivo . Mol Imaging Biol 13, 1204–1214 (2011). https://doi.org/10.1007/s11307-010-0439-1
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DOI: https://doi.org/10.1007/s11307-010-0439-1