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European Heart Journal Advance Access originally published online on August 3, 2007
European Heart Journal 2007 28(17):2172; doi:10.1093/eurheartj/ehm125
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© The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Cell quality in the ASTAMI study

Torstein Egeland

Section of Transplantation Immunology
Institute of Immunology
Rikshospitalet Medical Center
Sognsvannsveien 20
Oslo 0027
Norway

Jan E. Brinchmann

Ex Vivo Cell Laboratory
Institute of Immunology
Rikshospitalet Medical Center
Sognsvannsveien
Oslo 0027
Norway

Tel: +47 2307 1379 Fax: +47 2307 3780 E-mail address: torstein.egeland{at}rikshospitalet.no

Schächinger et al.1 recently reported clinical improvement after treatment of acute myocardial infarction with intracoronary injection of autologous bone-marrow-derived mononuclear cells (MNCs) (the REPAIR-AMI Trial). Here, the authors discuss whether lack of improvement in global left ventricular function in our study, the ASTAMI study,2 could be related to impaired cell quality or insufficient cell numbers. We believe this is unlikely for the following reasons:

  1. Comparable density gradient centrifugation techniques have been used for isolation of MNCs in the REPAIR-AMI and the ASTAMI studies. The density gradient solutions used for MNC separation, LymphoprepTM and Ficoll-Hypaque (Ficoll-PaqueTM), contain ficoll and sodium diatrizoate at identical concentrations.
  2. In the ASTAMI study, MNCs were kept at 4–8ºC overnight in 0.9% NaCl and 20% autologous heparin plasma, cell concentration <107 cells/ml. Cold saline-plasma storage of bone marrow or peripheral blood stem cells (PBSCs) for transplantation is being used worldwide for intercontinental transportation or prior to cryopreservation the following morning. To mention one of several examples: over the past 12 years, 163 multiple myeloma patients have received autologous PBSC transplantation in our hospital. PBSCs had been stored overnight at 4–8ºC in saline-plasma prior to cryopreservation. Stem cell engraftment occurred in >90% of the patients within 3 weeks and for the rest within the next few weeks.
  3. In the ASTAMI study, only MNCs with cell viability >90% were injected. The acridine orange/ethidium bromide technique was used for viability assessment; a sensitive, reliable, and reproducible method utilized for numerous viability tests, e.g. pre-transplant cell control and lymphocytotoxicity cross-match analyses.
  4. In parallel studies, functional assays on bone marrow MNCs from healthy controls, isolated and stored as for the ASTAMI patients, were shown to be normal by their numbers of the haematopoietic progenitor cell colonies CFU-GM and BFU-E (unpublished results).
  5. The relative number of isolated MNCs in the ASTAMI study was comparable to other studies. In addition, injected cell numbers have not been shown to correlate to changes in cardiac function.
Taken together, the cell-processing protocol in the ASTAMI study produces MNCs that are viable and functional. Whether intracoronary injection of autologous bone marrow MNCs has a beneficial effect still remains to be confirmed.

References

  1. Schächinger V, Erbs S, Elsässer A, Haberbosch W, Hambrecht R, Hölschermann H, Yu J, Corti R, Mathey DG, Hamm CW, Süselbeck T, Werner N, Haase J, Neuzner J, Germing A, Mark B, Assmus B, Tonn T, Dimmeler S, Zeiher AM. Improved clinical outcome after intracoronary administration of bone-marrow-derived progenitor cells in acute myocardial infarction: final 1-year results of the REPAIR-AMI trial. Eur Heart J (2006) 27:2775–2783.[Abstract/Free Full Text]
  2. Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, Egeland T, Endresen K, Ilebekk A, Mangschau A, Fjeld JG, Smith HJ, Taraldsrud E, Grogaard HK, Bjornerheim R, Brekke M, Muller C, Hopp E, Ragnarsson A, Brinchmann JE, Forfang K. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med (2006) 355:1199–1209.[Abstract/Free Full Text]

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 J Am Coll CardiolHome page
K. Lunde, S. Solheim, K. Forfang, H. Arnesen, L. Brinch, R. Bjornerheim, A. Ragnarsson, T. Egeland, K. Endresen, A. Ilebekk, et al.
Anterior myocardial infarction with acute percutaneous coronary intervention and intracoronary injection of autologous mononuclear bone marrow cells: safety, clinical outcome, and serial changes in left ventricular function during 12-months' follow-up.
J. Am. Coll. Cardiol., February 12, 2008; 51(6): 674 - 676.
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