Eur J Nucl Med Mol Imaging (2008) 35:1929–1930 DOI 10.1007/s00259-008-0865-3
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Early myocardial engraftment of autologous CD34+ cells administered transcoronary via a physiological cell-delivery system Piotr Musialek & Magdalena Kostkiewicz & R. Pawel Banys & Lukasz Tekieli & Marcin Majka & Mieczyslaw Pasowicz & Wieslawa Tracz
Received: 25 May 2008 / Accepted: 1 June 2008 / Published online: 6 August 2008 # Springer-Verlag 2008
Nuclear imaging has an essential role in guiding cell therapy from preclinical to clinical applications [1] but has thus far been used to a limited extent [2]. We employed single-photon emission computed tomography (SPECT) for high-sensitivity [1] visualization of early retention of labeled CD34+ cells delivered with conventional stop-flow technique (infusion via the central lumen of coronary-occlusive overthe-wire balloon catheter, IB) or via a cell-delivery perfusion catheter that we developed to direct the cells towards endothelium while maintaining coronary flow (IIB). Work supported by PBZ-KBN-099/P05/2003. P. Musialek (*) : M. Kostkiewicz : L. Tekieli : W. Tracz Department of Cardiac and Vascular Diseases, Jagiellonian University, Kraków, Poland e-mail:
[email protected] M. Majka Department of Transplantation, Jagiellonian University, Kraków, Poland P. Musialek : M. Kostkiewicz : R. P. Banys : L. Tekieli : M. Pasowicz : W. Tracz John Paul II Hospital, Kraków, Poland
Myocardial perfusion scintigraphy (99mTc-MIBI, images from two patients 7 days after a large anterior myocardial infarction in IA1–3 and IIA1–3) demonstrated an anteroseptal/antero-apical no-perfusion zone surrounded by infarct border zone (arrows). Two days later, autologous CD34+ cells (3.7×106 and 3.5×106) were selected immunomagnetically from bone marrow aspirates, labelled with 99 Tc-hexamethyl-propylene-amine-oxime and injected into the infarct-related artery: I, conventionally via the occlusive catheter [2, 3], and II, via the cell-delivery perfusion catheter. SPECT (IC1–3 and IIC1–3), performed 1 h later, indicated preferential cells’ retention in the infarct border zone (integrated images in ID1–3 and IID1–3, perfusion in grey scale). The proportion of radioactivity detected in myocardium (indicating percentage of myocardial engraftment) was 2.72% (I) and 7.26% (II). The physiological migration process requires cells’ rolling in contact with arterial endothelium in the presence of coronary flow [4], a step that is mandatory for subsequent adhesion and extravasation to the injury zone [4]. While the stop-flow technique (IB) has been adopted universally [2, 3] for transcoronary cell delivery, it was never shown to be required or effective in enhancing cells’ retention [3]. In addition, the ‘waterfall’ effect of balloon inflations/deflations [5] can contribute to cells’ wash-out.
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References 1. Bengel FM, Schachinger V, Dimmeler S. Cell-based therapies and imaging in cardiology. Eur J Nucl Med Mol Imaging 2005;32:S404–16. 2. Lipinski MJ, Biondi-Zoccai GGL, Abbate A, Khianey R, Sheiba I, Bartunek J, et al. Impact of intracoronary cell therapy on left ventricular function in the setting of acute myocardial infarction. A collaborative systematic review and meta-analysis of controlled clinical trials. J Am Coll Cardiol 2007;50:1761–7.
Eur J Nucl Med Mol Imaging (2008) 35:1929–1930
3. Wollert KC, Drexler H. Clinical applications of stem cells for the heart. Circ Res 2005;96:151–3. 4. Imhof BA, Aurrand-Lions M. Adhesion mechanisms regulating the migration of monocytes. Nature Rev Immunol 2004;4:432–44. 5. Kiyooka T, Hiramatsu O, Shigeto F, Nakamoto H, Tachibana H, Yada T, et al. Direct observation of epicardial coronary hemodynamics during reactive hyperemia and during adenosine administration by intravital video microscopy. Am J Physiol 2005;288:1437–43.
