LOGIN TO YOUR ACCOUNT

Username
Password
Remember Me
Or use your Academic/Social account:

CREATE AN ACCOUNT

Or use your Academic/Social account:

Congratulations!

You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.

Important!

Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message

CREATE AN ACCOUNT

Name:
Username:
Password:
Verify Password:
E-mail:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Markides, Hareklea; Kehoe, Oksana; Morris, Robert H; El Haj, Alicia J (2013)
Publisher: BioMed Central
Journal: Stem Cell Research & Therapy
Languages: English
Types: Article
Subjects: Research, R1
INTRODUCTION: The application of mesenchymal stem cells (MSCs) in treating rheumatoid arthritis (RA) has been made possible by the immunosuppressive and differentiation abilities of these cells. A non-invasive means of assessing cell integration and bio-distribution is fundamental in evaluating the risks and success of this therapy, thereby enabling clinical translation. This paper defines the use of superparamagnetic iron oxide nanoparticles (SPIONs) in conjunction with magnetic resonance imaging (MRI) to image and track MSCs in vivo within a murine model of RA. METHODS: Murine MSCs (mMSCs) were isolated, expanded and labelled with SiMAG, a commercially available particle. In vitro MRI visibility thresholds were investigated by labelling mMSCs with SiMAG with concentrations ranging from 0 to 10 μg/ml and resuspending varying cell doses (10930 to 5 × 10950 cells) in 2 mg/ml collagen prior to MR-imaging. Similarly, in vivo detection thresholds were identified by implanting 3 × 10950 mMSCs labelled with 0 to 10 μg/ml SiMAG within the synovial cavity of a mouse and MR-imaging. Upon RA induction, 300,000 mMSCs labelled with SiMAG (10 μg/ml) were implanted via intra-articular injection and joint swelling monitored as an indication of RA development over seven days. Furthermore, the effect of SiMAG on cell viability, proliferation and differentiation was investigated. RESULTS: A minimum particle concentration of 1 μg/ml (300,000 cells) and cell dose of 100,000 cells (5 and 10 μg/ml) were identified as the in vitro MRI detection threshold. Cell viability, proliferation and differentiation capabilities were not affected, with labelled populations undergoing successful differentiation down osteogenic and adipogenic lineages. A significant decrease (P < 0.01) in joint swelling was measured in groups containing SiMAG-labelled and unlabelled mMSCs implying that the presence of SPIONs does not affect the immunomodulating properties of the cells. In vivo MRI scans demonstrated good contrast and the identification of SiMAG-labelled populations within the synovial joint up to 7 days post implantation. This was further confirmed using histological analysis. CONCLUSIONS: We have been able to monitor and track the migration of stem cell populations within the rheumatic joint in a non-invasive manner. This manuscript goes further to highlight the key characteristics (biocompatible and the ability to create significant contrast at realistic doses within a clinical relevant system) demonstrated by SiMAG that should be incorporated into the design of a new clinically approved tracking agent.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • 1. Ringe J, Sittinger M: Tissue engineering in the rheumatic diseases. Arthritis Res Ther 2009, 11:211.
    • 2. Kastrinaki MC, Sidiropoulos P, Roche S, Ringe J, Lehmann S, Kritikos H, Vlahava VM, Delorme B, Eliopoulos GD, Jorgensen C, Charbord P, Haupl T, Boumpas DT, Papadaki HA: Functional, molecular and proteomic characterisation of bone marrow mesenchymal stem cells in rheumatoid arthritis. Ann Rheum Dis 2008, 67:741-749.
    • 3. Beckmann N, Falk R, Zurbrugg S, Dawson J, Engelhardt P: Macrophage infiltration into the rat knee detected by MRI in a model of antigen-induced arthritis. Magn Reson Med 2003, 49:1047-1055.
    • 4. Andreas K, Lubke C, Haupl T, Dehne T, Morawietz L, Ringe J, Sittinger M: Key regulatory molecules of cartilage destruction in rheumatoid arthritis: an in vitro study. Arthritis Res Ther 2008, 10:R9.
    • 5. Rindfleisch JA, Muller D: Diagnosis and management of rheumatoid arthritis. Am Fam Physician 2005, 72:1037-1047.
    • 6. Dazzi F, van Laar J, Cope A, Tyndall A: Cell therapy for autoimmune diseases. Arthritis Res Ther 2007, 9:206.
    • 7. Bouffi C, Djouad F, Mathieu M, Noël D, Jorgensen C: Multipotent mesenchymal stromal cells and rheumatoid arthritis: risk or benefit? Rheumatology 2009, 48:1185-1189.
    • 8. Ito A, Hibino E, Honda H, Hata K-i, Kagami H, Ueda M, Kobayashi T: A new methodology of mesenchymal stem cell expansion using magnetic nanoparticles. Bio Eng J 2004, 20:119-125.
    • 9. Chamberlain G, Fox J, Ashton B, Middleton J: Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells 2007, 25:2739-2749.
    • 10. Chen Y, Shao JZ, Xiang LX, Dong XJ, Zhang GR: Mesenchymal stem cells: a promising candidate in regenerative medicine. Int J Biochem Cell Biol 2008, 40:815-820.
    • 11. Jones BJ, McTaggart SJ: Immunosuppression by mesenchymal stromal cells: from culture to clinic. Exp Hematol 2008, 36:733-741.
    • 12. Zhou R, Acton PD, Ferrari VA: Imaging stem cells implanted in infarcted myocardium. J Am Coll Cardiol 2006, 48:2094-2106.
    • 13. Chen J, Wang F, Zhang Y, Jin X, Zhang L, Feng Y, Lin X, Yang L: In vivo tracking of superparamagnetic iron oxide nanoparticle labeled chondrocytes in large animal model. Ann Biomed Eng 2012, 19:19.
    • 14. Liu W, Frank JA: Detection and quantification of magnetically labeled cells by cellular MRI. Eur J Radiol 2009, 70:258-264.
    • 15. Himmelreich U, Dresselaers T: Cell labeling and tracking for experimental models using magnetic resonance imaging. Methods 2009, 48:112-124.
    • 16. Jing YH, Yang L, Duan XJ, Xie B, Chen W, Li Z, Tan HB: In vivo MR imaging tracking of magnetic iron oxide nanoparticle labeled, engineered, autologous bone marrow mesenchymal stem cells following intra-articular injection. Joint Bone Spine 2008, 75:432-438.
    • 17. Ferreira L: Nanoparticles as tools to study and control stem cells. J Cell Biochem 2009, 108:746-752.
    • 18. Chen YC, Hsiao JK, Liu HM, Lai IY, Yao M, Hsu SC, Ko BS, Chen YC, Yang CS, Huang DM: The inhibitory effect of superparamagnetic iron oxide nanoparticle (Ferucarbotran) on osteogenic differentiation and its signaling mechanism in human mesenchymal stem cells. Toxicol Appl Pharmacol 2010, 245:272-279.
    • 19. Saldanha KJ, Doan RP, Ainslie KM, Desai TA, Majumdar S: Micrometer-sized iron oxide particle labeling of mesenchymal stem cells for magnetic resonance imaging-based monitoring of cartilage tissue engineering. Magn Reson Imaging 2011, 29:40-49.
    • 20. Budde MD, Frank JA: Magnetic tagging of therapeutic cells for MRI. J Nucl Med 2009, 50:171-174.
    • 21. Golovko DM, Henning T, Bauer JS, Settles M, Frenzel T, Mayerhofer A, Rummeny EJ, Daldrup-Link HE: Accelerated stem cell labeling with ferucarbotran and protamine. Eur Radiol 2010, 20:640-648.
    • 22. He G, Zhang H, Wei H, Wang Y, Zhang X, Tang Y, Wei Y, Hu S: In vivo imaging of bone marrow mesenchymal stem cells transplanted into myocardium using magnetic resonance imaging: a novel method to the transplanted cells. Int J Cardiol 2007, 114:4-10.
    • 23. Hill JM, Dick AJ, Raman VK, Thompson RB, Yu ZX, Hinds KA, Pessanha BS, Guttman MA, Varney TR, Martin BJ, Dunbar CE, McVeigh ER, Lederman RJ: Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells. Circulation 2003, 108:1009-1014.
    • 24. Kim TH, Kim JK, Shim W, Kim SY, Park TJ, Jung JY: Tracking of transplanted mesenchymal stem cells labeled with fluorescent magnetic nanoparticle in liver cirrhosis rat model with 3-T MRI. Magn Reson Imaging 2010, 28:1004-1013.
    • 25. Heymer A, Haddad D, Weber M, Gbureck U, Jakob PM, Eulert J, Nöth U: Iron oxide labelling of human mesenchymal stem cells in collagen hydrogels for articular cartilage repair. Biomaterials 2008, 29:1473-1483.
    • 26. Chamberlain G, Wright K, Rot A, Ashton B, Middleton J: Murine mesenchymal stem cells exhibit a restricted repertoire of functional chemokine receptors: comparison with human. Plos One 2008, 3:e2934.
    • 27. Nowell MA, Richards PJ, Horiuchi S, Yamamoto N, Rose-John S, Topley N, Williams AS, Jones SA: Soluble IL-6 receptor governs IL-6 activity in experimental arthritis: blockade of arthritis severity by soluble glycoprotein 130. J Immunol 2003, 171:3202-3209.
    • 28. Kim HS, Oh SY, Joo HJ, Son KR, Song IC, Moon WK: The effects of clinically used MRI contrast agents on the biological properties of human mesenchymal stem cells. NMR Biomed 2010, 23:514-522.
    • 29. Henning TD, Sutton EJ, Kim A, Golovko D, Horvai A, Ackerman L, Sennino B, McDonald D, Lotz J, Daldrup-Link HE: The influence of ferucarbotran on the chondrogenesis of human mesenchymal stem cells. Contrast Media Mol Imaging 2009, 4:165-173.
    • 30. Jasmin, Torres AL, Nunes HM, Passipieri JA, Jelicks LA, Gasparetto EL, Spray DC, Campos de Carvalho AC, Mendez-Otero R: Optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and in vivo visualization by magnetic resonance imaging. J Nanobiotechnology 2011, 9:4.
    • 31. Farrell E, Wielopolski P, Pavljasevic P, Kops N, Weinans H, Bernsen MR, van Osch GJVM: Cell labelling with superparamagnetic iron oxide has no effect on chondrocyte behaviour. Osteoarthritis Cartilage 2009, 17:961-967.
    • 32. LaConte L, Nitin N, Bao G: Magnetic nanoparticle probes. Materials Today 2005, 8:32-38.
    • 33. Hofmann-Amtenbrink M, Hofmann H, Montet X: Superparamagnetic nanoparticles - a tool for early diagnostics. Swiss Med Wkly 2010, 140:7-13.
    • 34. Markides H, Rotherham M, El Haj AJ: Biocompatibility and toxicity of magnetic nanoparticles in regenerative medicine. J Nanomaterials 2012, 2012:11.
    • 35. Pardoe H, Chua-anusorn W, St. Pierre TG, Dobson J: Structural and magnetic properties of nanoscale iron oxide particles synthesized in the presence of dextran or polyvinyl alcohol. J Magn Magn Mater 2001, 22:41.
    • 36. Khurana A, Nejadnik H, Chapelin F, Lenkov O, Gawande R, Lee S, Gupta SN, Aflakian N, Derugin N, Messing S, Lin G, Lue TF, Pisani L, Daldrup-Link HE: Ferumoxytol: a new, clinically applicable label for stem-cell tracking in arthritic joints with MRI. Nanomedicine (Lond) 2013. in press.
    • 37. Henning TD, Gawande R, Khurana A, Tavri S, Mandrussow L, Golovko D, Horvai A, Sennino B, McDonald D, Meier R, Wendland M, Derugin N, Link TM, Daldrup-Link HE: Magnetic resonance imaging of ferumoxide-labeled mesenchymal stem cells in cartilage defects: in vitro and in vivo investigations. Mol Imaging 2012, 11:197-209.
    • 38. Hughes S, El Haj AJ, Dobson J: Magnetic micro- and nanoparticle mediated activation of mechanosensitive ion channels. Med Eng Phys 2005, 27:754-762.
    • 39. Dousset V, Tourdias T, Brochet B, Boiziau C, Petry KG: How to trace stem cells for MRI evaluation? J Neurol Sci 2008, 265:122-126.
    • 40. Kostura L, Kraitchman DL, Mackay AM, Pittenger MF, Bulte JWM: Feridex labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis. NMR Biomed 2004, 17:513-517.
    • 41. Bendele A: Animal models of rheumatoid arthritis. J Musculoskelet Neuronal Interact 2001, 1:377-385.
    • 42. Henderson IJ, Tuy B, Connell D, Oakes B, Hettwer WH: Prospective clinical study of autologous chondrocyte implantation and correlation with MRI at three and 12 months. J Bone Joint Surg Br 2003, 85:1060-1066.
  • No related research data.
  • Discovered through pilot similarity algorithms. Send us your feedback.

Share - Bookmark

Cite this article