Skip to main content
SpringerLink
Log in

Multimodality molecular imaging in cardiac regenerative therapy

  • Molecular Imaging Corner
  • Published:
Journal of Nuclear Cardiology Aims and scope

Abstract

Stem cell therapy holds great promise for the repair and regeneration of damaged myocardium. Disappointing results from recent large-scale randomized trials using adult stem cells, however, have led some to question the efficacy of this new therapeutic. Because most clinical stem cell trials have not incorporated molecular imaging to track cell fate, it may be premature to abandon this approach. Herein, we will review how multimodality imaging can be incorporated into cardiac regenerative therapy to facilitate the translation of stem cell therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1

Similar content being viewed by others

Abbreviations

BLI:

Bioluminescence imaging

FLI:

Fluorescence imaging

HSVttk:

Herpes simplex virus truncated thymidine kinase

MRI:

Magnetic resonance imaging

PET:

Positron emission tomography (PET)

RFP:

Red fluorescent protein

SPECT:

Single-photon emission computed tomography

References

  1. Writing Group M, Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ et al. Heart disease and stroke statistics-2016 update: A report from the American Heart Association. Circulation. 2016;133:e38-360.

  2. Nguyen PK, Rhee JW, Wu JC. Adult stem cell therapy and heart failure, 2000 to 2016: A systematic review. JAMA Cardiol. 2016;1:831-41.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Liang G, Nguyen PK. Molecular probes for cardiovascular imaging. J Nucl Cardiol. 2016;23:783-9.

    Article  PubMed  Google Scholar 

  4. Yaghoubi SS, Campbell DO, Radu CG, Czernin J. Positron emission tomography reporter genes and reporter probes: Gene and cell therapy applications. Theranostics. 2012;2:374-91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Nguyen PK, Riegler J, Wu JC. Stem cell imaging: From bench to bedside. Cell Stem Cell. 2014;14:431-44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chen IY, Wu JC. Molecular imaging: The key to advancing cardiac stem cell therapy. Trends Cardiovasc Med. 2013;23:201-10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Nguyen PK, Lan F, Wang Y, Wu JC. Imaging: Guiding the clinical translation of cardiac stem cell therapy. Circ Res. 2011;109:962-79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hou D, Youssef EA, Brinton TJ, Zhang P, Rogers P, Price ET et al. Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials. Circulation. 2005;112:I150-6.

    PubMed  Google Scholar 

  9. Pearl JI, Lee AS, Leveson-Gower DB, Sun N, Ghosh Z, Lan F et al. Short-term immunosuppression promotes engraftment of embryonic and induced pluripotent stem cells. Cell Stem Cell. 2011;8:309-17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hu S, Huang M, Nguyen PK, Gong Y, Li Z, Jia F et al. Novel microRNA prosurvival cocktail for improving engraftment and function of cardiac progenitor cell transplantation. Circulation. 2011;124:S27-34.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Riegler J, Gillich A, Shen Q, Gold JD, Wu JC. Cardiac tissue slice transplantation as a model to assess tissue-engineered graft thickness, survival, and function. Circulation. 2014;130:S77-86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Riegler J, Tiburcy M, Ebert A, Tzatzalos E, Raaz U, Abilez OJ et al. Human engineered heart muscles engraft and survive long term in a rodent myocardial infarction model. Circ Res. 2015;117:720-30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lee AS, Xu D, Plews JR, Nguyen PK, Nag D, Lyons JK et al. Preclinical derivation and imaging of autologously transplanted canine induced pluripotent stem cells. J Biol Chem. 2011;286:32697-704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Parashurama N, Ahn BC, Ziv K, Ito K, Paulmurugan R, Willmann JK et al. Multimodality molecular imaging of cardiac cell transplantation: Part II. In vivo imaging of bone marrow stromal cells in swine with PET/CT and MR imaging. Radiology. 2016;280:826-36.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Nguyen PK, Neofytou E, Rhee JW, Wu JC. Potential strategies to address the major clinical barriers facing stem cell regenerative therapy for cardiovascular disease: A review. JAMA Cardiol. 2016;1(8):953-62.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Riegler J, Ebert A, Qin X, Shen Q, Wang M, Ameen M et al. Comparison of magnetic resonance imaging and serum biomarkers for detection of human pluripotent stem cell-derived teratomas. Stem Cell Rep. 2016;6:176-87.

    Article  CAS  Google Scholar 

  17. Kotini AG, de Stanchina E, Themeli M, Sadelain M, Papapetrou EP. Escape mutations, ganciclovir resistance, and teratoma formation in human iPSCs expressing an HSVtk suicide gene. Mol Ther Nucleic Acids. 2016;5:e284.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chong JJ, Yang X, Don CW, Minami E, Liu YW, Weyers JJ et al. Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature. 2014;510:273-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Vrtovec B, Poglajen G, Lezaic L, Sever M, Socan A, Domanovic D et al. Comparison of transendocardial and intracoronary CD34+ cell transplantation in patients with nonischemic dilated cardiomyopathy. Circulation. 2013;128:S42-9.

    Article  CAS  PubMed  Google Scholar 

  20. Hofmann M, Wollert KC, Meyer GP, Menke A, Arseniev L, Hertenstein B et al. Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation. 2005;111:2198-202.

    Article  PubMed  Google Scholar 

  21. Karpov RS, Popov SV, Markov VA, Suslova TE, Ryabov VV, Poponina YS et al. Autologous mononuclear bone marrow cells during reparative regeneration after acute myocardial infarction. Bull Exp Biol Med. 2005;140:640-3.

    Article  CAS  PubMed  Google Scholar 

  22. Blocklet D, Toungouz M, Berkenboom G, Lambermont M, Unger P, Preumont N et al. Myocardial homing of nonmobilized peripheral-blood CD34+ cells after intracoronary injection. Stem Cells. 2006;24:333-6.

    Article  PubMed  Google Scholar 

  23. Goussetis E, Manginas A, Koutelou M, Peristeri I, Theodosaki M, Kollaros N et al. Intracoronary infusion of CD133+ and CD133-CD34+ selected autologous bone marrow progenitor cells in patients with chronic ischemic cardiomyopathy: Cell isolation, adherence to the infarcted area, and body distribution. Stem Cells. 2006;24:2279-83.

    Article  CAS  PubMed  Google Scholar 

  24. Kang WJ, Kang HJ, Kim HS, Chung JK, Lee MC, Lee DS. Tissue distribution of 18F-FDG-labeled peripheral hematopoietic stem cells after intracoronary administration in patients with myocardial infarction. J Nucl Med. 2006;47:1295-301.

    PubMed  Google Scholar 

  25. Penicka M, Lang O, Widimsky P, Kobylka P, Kozak T, Vanek T et al. One-day kinetics of myocardial engraftment after intracoronary injection of bone marrow mononuclear cells in patients with acute and chronic myocardial infarction. Heart. 2007;93:837-41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Schachinger V, Aicher A, Dobert N, Rover R, Diener J, Fichtlscherer S et al. Pilot trial on determinants of progenitor cell recruitment to the infarcted human myocardium. Circulation. 2008;118:1425-32.

    Article  PubMed  Google Scholar 

  27. Silva SA, Sousa AL, Haddad AF, Azevedo JC, Soares VE, Peixoto CM et al. Autologous bone-marrow mononuclear cell transplantation after acute myocardial infarction: Comparison of two delivery techniques. Cell Transpl. 2009;18:343-52.

    Article  Google Scholar 

  28. Barbosa da Fonseca LM, Gutfilen B, Rosado de Castro PH, Battistella V, Goldenberg RC, Kasai-Brunswick T et al. Migration and homing of bone-marrow mononuclear cells in chronic ischemic stroke after intra-arterial injection. Exp Neurol 2010;221:122-8.

  29. Barbosa da Fonseca LM, Xavier SS, Rosado de Castro PH, Lima RS, Gutfilen B, Goldenberg RC et al. Biodistribution of bone marrow mononuclear cells in chronic chagasic cardiomyopathy after intracoronary injection. Int J Cardiol 2011;149:310-4.

Download references

Disclosure

None.

Author information

Authors and Affiliations

  1. Division of Cardiovascular Medicine, Department of Medicine, Stanford University, 300 Pasteur Drive, Stanford, CA, 94305, USA

    Davis Vo BS & Patricia K. Nguyen MD

  2. Cardiology Section, Department of Medicine, Veterans Affairs, 3801 Miranda Ave, Palo Alto, CA, 94304, USA

    Davis Vo BS & Patricia K. Nguyen MD

  3. Stanford University, 300 Pasteur Drive, Grant Building, S114, Stanford, CA, 94305-5208, USA

    Patricia K. Nguyen MD

Authors
  1. Davis Vo BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patricia K. Nguyen MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patricia K. Nguyen MD.

Additional information

The authors of this article have provided a PowerPoint file, available for download at SpringerLink, which summarises the contents of the paper and is free for re-use at meetings and presentations. Search for the article DOI on www.SpringerLink.com

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PPTX 1256 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vo, D., Nguyen, P.K. Multimodality molecular imaging in cardiac regenerative therapy. J. Nucl. Cardiol. 24, 1803–1809 (2017). https://doi.org/10.1007/s12350-017-0785-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12350-017-0785-3

Keywords

Search

Navigation