In Vivo Imaging of Regenerated Tissue: State of Art and Future Perspectives

  • Vincenzo Lionetti
  • Alessandro Pingitore
Part of the Updates in Surgery book series (UPDATESSURG, volume 0)


Mesenchymal stem cells (MSCs) are multipotent cells which can give rise to mesenchymal and nonmesenchymal tissues in vitro and in vivo [1]. The distribution of resident MSCs throughout the post-natal organism is mainly related to their existence in perivascular niches [2]. They can differentiate into osteogenic, adipogenic, chondrogenic, myocardial, or neural lineages when exposed to specific stimuli, making them attractive for tissue regeneration [3, 4]. Emerging evidence has shown that MSC transplantation offers a means to stimulate tissue repair either by direct (exogenous) or indirect (endogenous) cell replacement or angiogenesis [5, 6]. In fact, exogenous MSCs have shown the ability to support a paracrine activation of endogenous stem cells for tissue repair by secreting chemokines, as stromal derived factor-1 alpha (SDF-1α), and/or growth factors, as vascular endothelial growth factor. Despite the rapid research advancement, possible tissue repair by adult stem cell therapy is currently hampered in vivo by poor cell viability and delivery efficiency, uncertain differentiating fate, and therefore the use of this approach has raised a number of bioethical questions [7]. Hence, the strong need for more effective therapeutic approaches emphasizing the physiological plasticity of postnatal organs following an injury [8, 9], and more accurate imaging methods to allow a long-term in vivo monitoring of tissue regeneration [10]. Indeed, one of the most important accomplishments of modern physiology is the development of imaging techniques able to explore biochemical/molecular processes in the intact organism, i.e. in the absence of confounding effects inevitably caused by invasive procedures or ex vivo experimental prepar


Single Photon Emission Compute Tomography Positron Emission Tomo Myocar Dial Vivo Image Enerated Tissue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Bernardo ME, Locatelli F, Fibbe WE (2009) Mesenchymal stromal cells. Ann N Y Acad Sci 1176:101–117CrossRefPubMedGoogle Scholar
  2. 2.
    da Silva Meirelles L, Caplan AI, Nardi NB (2008) In search of the in vivo identity of mesenchymal stem cells. Stem Cells 26:2287–2299CrossRefPubMedGoogle Scholar
  3. 3.
    Benayahu D, Shefer G, Shur I (2009) Insights into chromatin remodelers in mesenchymal stem cells and differentiation. Front Biosci 14:398–409PubMedGoogle Scholar
  4. 4.
    Ventura C, Cavallini C, Bianchi F et al (2008) Stem cells and cardiovascular repair: a role for natural and synthetic molecules harboring differentiating and paracrine logics. Cardiovasc Hematol Agents Med Chem 6:60–68CrossRefPubMedGoogle Scholar
  5. 5.
    Anversa P, Leri A, Rota M et al (2007) Concise review: stem cells, myocardial regeneration, and methodological artifacts. Stem Cells 25:589–601CrossRefPubMedGoogle Scholar
  6. 6.
    Gnecchi M, Zhang Z, Ni A et al (2008) Paracrine mechanisms in adult stem cell signaling and therapy. Circ Res 103:1204–1219CrossRefPubMedGoogle Scholar
  7. 7.
    Hyun I (2010) The bioethics of stem cell research and therapy. J Clin Invest 120:71–75CrossRefPubMedGoogle Scholar
  8. 8.
    Lionetti V, Cantoni S, Cavallini C et al (2010) Hyaluronan mixed esters of butyric and retinoic acid affording myocardial survival and repair without stem cell transplantation. J Biol Chem 285:9949–9961CrossRefPubMedGoogle Scholar
  9. 9.
    Forini F, Lionetti V, Ardehali H et al (2010) Early long-term L-T3 replacement rescues mitochondria and prevents ischemic cardiac remodeling in rats. J Cell Mol Med doi: 10.1111/j.1582-4934.2010.01014Google Scholar
  10. 10.
    Lee Z, Dennis JE, Gerson SL (2008) Imaging stem cell implant for cellular-based therapies. Exp Biol Med (Maywood) 233:930–940CrossRefGoogle Scholar
  11. 11.
    Leong-Poi H (2009) Molecular imaging using contrast-enhanced ultrasound: evaluation of angiogenesis and cell therapy. Cardiovasc Res 84:190–200CrossRefPubMedGoogle Scholar
  12. 12.
    Agrawal V, Johnson SA, Reing J et al (2010) Epimorphic regeneration approach to tissue replacement in adult mammals. Proc Natl Acad Sci U S A 107:3351–3355CrossRefPubMedGoogle Scholar
  13. 13.
    Kilarski WW, Samolov B, Petersson L et al (2009) Biomechanical regulation of blood vessel growth during tissue vascularization. Nat Med 15:657–664CrossRefPubMedGoogle Scholar
  14. 14.
    Schröter G, Schneider-Eicke J, Schwaiger M (1994) Assessment of tissue viability with fluorine-18-fluoro-2-deoxyglucose (FDG) and carbon-11-acetate PET imaging. Herz 19:42–50PubMedGoogle Scholar
  15. 15.
    Endo M, Yoshida K, Iinuma TA et al (1987) Noninvasive quantification of regional myocardial blood flow and ammonia extraction fraction using nitrogen-13 ammonia and positron emission tomography. Ann Nucl Med 1:1–6CrossRefPubMedGoogle Scholar
  16. 16.
    Grierson JR, Shields AF (2000) Radiosynthesis of 3′-deoxy-3′-fluoro-thymidine: 18F-FLT for imaging cellular proliferation in vivo. Nucl Med Biol 27:143–156CrossRefPubMedGoogle Scholar
  17. 17.
    Kendziorra K, Barthel H, Erbs S et al (2008) Effect of progenitor cells on myocardial perfusion and metabolism in patients after recanalization of a chronically occluded coronary artery. J Nucl Med 49:557–563CrossRefPubMedGoogle Scholar
  18. 18.
    Jackson J, Chapon C, Jones W et al (2009) In vivo multimodal imaging of stem cell transplantation in a rodent model of Parkinson’s disease. J Neurosci Methods 183:141–148CrossRefPubMedGoogle Scholar
  19. 19.
    Fuster V, Sanz J, Viles-Gonzalez JF et al (2006) The utility of magnetic resonance imaging in cardiac tissue regeneration trials. Nat Clin Pract Cardiovasc Med 1:S2–S7CrossRefGoogle Scholar
  20. 20.
    Watrin-Pinzano A, Ruaud JP, Cheli Y et al (2004) T2 mapping: an efficient MR quantitative technique to evaluate spontaneous cartilage repair in rat patella. Osteoarthritis Cartilage 12:191–200CrossRefPubMedGoogle Scholar
  21. 21.
    Filippi M, Agosta F (2009) Magnetic resonance techniques to quantify tissue damage, tissue repair, and functional cortical reorganization in multiple sclerosis. Prog Brain Res 175:465–482CrossRefPubMedGoogle Scholar
  22. 22.
    Raichle ME, Mintun MA (2006) Brain work and brain imaging. Annu Rev Neurosci 29:449–476CrossRefPubMedGoogle Scholar
  23. 23.
    Yen YF, Kohler SJ, Chen AP et al (2009) Imaging considerations for in vivo 13C metabolic mapping using hyperpolarized 13C-pyruvate. Magn Reson Med 62:1–10CrossRefPubMedGoogle Scholar
  24. 24.
    Pichler BJ, Wehrl HF, Kolb A et al (2009) Positron emission tomography/ magnetic resonance imaging: the next generation of multimodality imaging? Semin Nucl Med 38:199–208CrossRefGoogle Scholar
  25. 25.
    Hoffman JM, Gambhir SS (2007) Molecular imaging: the vision and opportunity for radiology in the future. Radiology 244:39–47CrossRefPubMedGoogle Scholar
  26. 26.
    Cormode DP, Skajaa T, Fayad ZA et al (2009) Nanotechnology in medical imaging: probe design and applications. Arterioscler Thromb Vasc Biol 29:992–1000CrossRefPubMedGoogle Scholar
  27. 27.
    Schroeder T (2008) Imaging stem-cell-driven regeneration in mammals. Nature 453:345–351CrossRefPubMedGoogle Scholar
  28. 28.
    Serganova I, Mayer-Kukuck P, Huang R et al (2008) Molecular imaging: reporter gene imaging. Handb Exp Pharmacol (185 Pt 2):167–223CrossRefPubMedGoogle Scholar
  29. 29.
    Lee SW, Padmanabhan P, Ray P et al (2009) Stem cell-mediated accelerated bone healing observed with in vivo molecular and small animal imaging technologies in a model of skeletal injury. J Orthop Res 27:295–302CrossRefPubMedGoogle Scholar
  30. 30.
    Wang X, Mao X, Xie L et al (2009) Involvement of Notch1 signaling in neurogenesis in the subventricular zone of normal and ischemic rat brain in vivo. J Cereb Blood Flow Metab 29:1644–1654CrossRefPubMedGoogle Scholar
  31. 31.
    Liu J, Cheng EC, Long RC et al (2009) Noninvasive monitoring of embryonic stem cells in vivo with MRI transgene reporter. Tissue Eng Part C Methods 15:739–747CrossRefPubMedGoogle Scholar
  32. 32.
    Lionetti V, Paddeu S (2010) Towards ultrasound molecular imaging. In: Paradossi G, Pellegretti P, Trucco A (Eds.): Ultrasound contrast agents: targeting and processing methods for theranostics. Springer-Verlag Italia, Milan, pp 1–11CrossRefGoogle Scholar
  33. 33.
    Corot C, Robert P, Iée JM et al (2006) Recent advances in iron oxide nanocrystal technology for medical imaging. Adv Drug Deliv Rev 58:1471–1504CrossRefPubMedGoogle Scholar
  34. 34.
    Lewin M, Carlesso N, Tung CH (2000) Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells. Nat Biotechnol 18:410–414CrossRefPubMedGoogle Scholar
  35. 35.
    Bulte JW, Douglas T, Witwer B (2001) Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. Nat Biotechnol 19:1141–1147CrossRefPubMedGoogle Scholar
  36. 36.
    Wang FH, Lee IH, Holmström N et al (2006) Magnetic resonance tracking of nanoparticle labelled neural stem cells in a rat’s spinal cord. Nanotechnology 17:191Google Scholar
  37. 37.
    Gilad AA, Ziv K, McMahon MT et al (2008) MRI reporter genes. J Nucl Med 49:1905–1908CrossRefPubMedGoogle Scholar
  38. 38.
    Ki S, Sugihara F, Kasahara K et al (2006) A novel magnetic resonance-based method to measure gene expression in living cells. Nucleic Acids Res 34:e51CrossRefGoogle Scholar
  39. 39.
    Pawelczyk E, Frank JA (2008) Transferrin receptor expression in iron oxide-labeled mesenchymal stem cells. Radiology 247:913CrossRefPubMedGoogle Scholar
  40. 40.
    Campan M, Lionetti V, Aquaro GD et al (2009) Stem cells transduction with ferritin as a reporter gene to track their fate by 1.5 Tesla MRI, in the beating heart. Circ Res 105:e62Google Scholar

Copyright information

© Springer-Verlag ItaliaSpringer-Verlag Italia 2011 2011

Authors and Affiliations

  • Vincenzo Lionetti
    • 1
  • Alessandro Pingitore
    • 2
  1. 1.Sector of MedicineScuola Superiore Sant’AnnaPisaItaly
  2. 2.Institute of Clinical PhysiologyCNR-Fondazione G. MonasterioPisaItaly

Personalised recommendations