Bone marrow stem cell imaging after intracoronary administration

Kurpisz, Maciej; Czepczyński, Rafał; Grygielska, Beata; Majewski, Michał; Fiszer, Dorota; Jerzykowska, Olga; Sowiński, Jerzy; Siminiak, Tomasz

doi:10.1016/j.ijcard.2006.08.062

Cited by 46 publications

(29 citation statements)

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“…With a similar labeling protocol, the 111 In radioactivity in the heart was reported to be 2.6%, 4.9%, and 11% in 3 patients treated with bone marrow-derived mononuclear cells 4 to 7 days after AMI. 16 Slightly lower incorporation (1.3% to 2.6%) was described in 3 patients who received bone marrow-derived cells labeled with FDG. 18 It has been discussed whether a different mode of application may further enhance cell homing.…”

Section: Schächinger Et Al Cpc Homing After MImentioning

confidence: 96%

“…Clinically, labeling of bone marrow-derived cells or isolated CD133 ϩ cells with the radiopharmaceutical 111 In-oxine was performed in several case reports in patients with AMI or chronic myocardial infarction. 16,17 Hofmann et al 18 infused bone marrow-derived cells or CD34 ϩ cells labeled with the PET tracer FDG into 3 patients with AMI. All experimental and clinical studies demonstrated a relatively low (ranging from 2% to 11%) acute accumulation of 111 In activity in the heart in patients treated with bone marrow-derived cells or CD133 ϩ cells.…”

Section: Clinical Perspective P 1432mentioning

confidence: 99%

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Pilot Trial on Determinants of Progenitor Cell Recruitment to the Infarcted Human Myocardium

et al. 2008

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Background-Clinical trials indicate a beneficial effect of intracoronary infusion of progenitor cells on myocardial function in patients with ischemic heart disease. The extent and potential determinants of proangiogenic progenitor cell homing into the damaged myocardium after intracoronary infusion and the underlying mechanisms are still unknown. Method and Results-Circulating proangiogenic progenitor cells isolated from peripheral blood and cultivated for 3 days were labeled with radioactive indium oxine ( 111 In-oxine). Radiolabeled proangiogenic progenitor cells (7.6Ϯ3.0 MBq, meanϮSD) were administered to patients with previous myocardial infarction and a revascularized infarct vessel at various stages after infarction (5 days to 17 years). Viability of the infarcted myocardium was determined by 18 F-fluorodeoxyglucose-positron emission tomography and microcirculatory function by intracoronary Doppler measurements. One hour after application of progenitor cells, a mean of 6.9Ϯ4.7% (range, 1% to 19%; nϭ17) of total radioactivity was detected in the heart, which declined to 2Ϯ1% after 3 to 4 days. Average activity within the first 24 hours was highest among patients with acute myocardial infarction (Յ14 days; 6.3Ϯ2.9%; nϭ8) and progressively decreased in patients treated in an intermediate phase (Ͼ14 days to 1 year; 4.5Ϯ3.2%; nϭ4) or a chronic stage (infarct age Ͼ1 year; 2.5Ϯ1.6%; nϭ5). Low viability of the infarcted myocardium and reduced coronary flow reserve were significant (PϽ0.05) predictors of proangiogenic progenitor cell homing. Conclusions-In patients after myocardial infarction undergoing intracoronary infusion of111 In-oxine-labeled proangiogenic progenitor cells, a substantial amount of radioactivity is detected for several days in the heart, indicating homing of progenitor cells to the myocardium. The amount of proangiogenic progenitor cells retained in the heart decreased progressively with time after the acute myocardial infarction. Proangiogenic progenitor cells preferentially home to extensive acute myocardial infarcts characterized by low viability and reduced coronary flow reserve. (Circulation.

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Section: Schächinger Et Al Cpc Homing After MImentioning

confidence: 96%

Section: Clinical Perspective P 1432mentioning

confidence: 99%

Pilot Trial on Determinants of Progenitor Cell Recruitment to the Infarcted Human Myocardium

et al. 2008

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“…Many studies have confirmed a significant contribution of the liver to stem cell absorption (Gao et al, 2001;Brenner et al, 2004;Hofmann et al, 2005;Blocklet et al, 2006;Freyman et al, 2006;Kang et al, 2006;Doyle et al, 2007;Kurpisz et al, 2007;Qian et al, 2007;Schachinger et al, 2008). Hofmann et al (2005) have shown that i.v.…”

Section: Dispersion and Clearancementioning

confidence: 96%

“…In fact, different kinetics were observed with G-CSFmobilized HSCs (Kang et al, 2006), circulating proangiogenic progenitor cells (Schachinger et al, 2008) and peripheral blood CD133 + cells (Caveliers et al, 2007). The spleen is another non-target organ that absorbs stem cells (Gao et al, 2001;Brenner et al, 2004;Hofmann et al, 2005;Blocklet et al, 2006;Doyle et al, 2007;Kurpisz et al, 2007;Qian et al, 2007;Schachinger et al, 2008). Early (1 h post administration), single-time-point observations showed that 17.3 Ϯ 1.1% and 17 Ϯ 6% of intracoronary injected BMNCs (Qian et al, 2007) and intraventricularly administered CD34…”

Section: Dispersion and Clearancementioning

confidence: 99%

Stem cell therapy for cardiovascular disease: the demise of alchemy and rise of pharmacology

Jadczyk

Faulkner

Madeddu

2013

British J Pharmacology

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Regenerative medicine holds great promise as a way of addressing the limitations of current treatments of ischaemic disease. In preclinical models, transplantation of different types of stem cells or progenitor cells results in improved recovery from ischaemia. Furthermore, experimental studies indicate that cell therapy influences a spectrum of processes, including neovascularization and cardiomyogenesis as well as inflammation, apoptosis and interstitial fibrosis. Thus, distinct strategies might be required for specific regenerative needs. Nonetheless, clinical studies have so far investigated a relatively small number of options, focusing mainly on the use of bone marrow-derived cells. Rapid clinical translation resulted in a number of small clinical trials that do not have sufficient power to address the therapeutic potential of the new approach. Moreover, full exploitation has been hindered so far by the absence of a solid theoretical framework and inadequate development plans. This article reviews the current knowledge on cell therapy and proposes a model theory for interpretation of experimental and clinical outcomes from a pharmacological perspective. Eventually, with an increased association between cell therapy and traditional pharmacotherapy, we will soon need to adopt a unified theory for understanding how the two practices additively interact for a patient's benefit. LINKED ARTICLESThis article is part of a themed section on Regenerative Medicine and Pharmacology: A Look to the Future. To view the other articles in this section visit http://dx

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“…Pilot studies suggested that selected BM CD34 + cells might exhibit higher engraftment capacity than nonselected BM mononuclear cells. 5,6 Nevertheless, animal and human studies with labeled progenitor cells have thus far included 1 to a maximum of 8 subjects with recent MI, [6][7][8][9][10][11][12][13] precluding any meaningful systematic analysis of the potential relationship between the extent of myocardial injury and cell uptake. On the contrary, pivotal clinical studies have used LVEF (typically ≤45%) as the main inclusion criterion and efficacy end point 5,6 in the absence of any evidence that cell uptake is related to the degree of LVEF impairment.…”

Section: Clinical Perspective On P 328mentioning

confidence: 99%

Infarct Size Determines Myocardial Uptake of CD34 ⁺ Cells in the Peri-Infarct Zone

Musiałek

Tekieli

Kostkiewicz

et al. 2013

Circ: Cardiovascular Imaging

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Background-Effective progenitor cell recruitment to the ischemic injury zone is a prerequisite for any potential therapeutic effect. Cell uptake determinants in humans with recent myocardial infarction are not defined. We tested the hypothesis that myocardial uptake of autologous CD34 + cells delivered via an intracoronary route after recent myocardial infarction is related to left ventricular (LV) ejection fraction (LVEF) and infarct size.Methods and Results-Thirty-one subjects (age, 36-69 years; 28 men) with primary percutaneous coronary interventiontreated anterior ST-segment-elevation myocardial infarction and significant myocardial injury (median peak troponin I, 138 ng/mL [limits, 58-356 ng/mL]) and sustained LVEF depression at ≤45% were recruited. On day 10 (days 7-12), 4.3×10 6 (0.7-9.9×10 6 ) 99m Tc-extametazime-labeled autologous bone marrow CD34 + cells (activity, MBq]) were administered transcoronarily (left anterior descending coronary artery).99m Tc-methoxyisobutyl isonitrile (99 m Tc-MIBI) single-photon emission computed tomography before cell delivery showed 7 (2-11) (of 17) segments with definitely abnormal/ absent perfusion. Late gadolinium-enhanced infarct core mass was 21.7 g (4.4-45.9 g), and infarct border zone mass was 29.8 g (3.9-60.2 g) (full-width at half-maximum, signal intensity thresholding algorithm). One hour after administration, 5.2% (1.7%-9.9%) of labeled cell activity localized in the myocardium (whole-body planar γ scan). Image fusion of labeled cell single-photon emission computed tomography with LV perfusion single-photon emission computed tomography or with cardiac magnetic resonance infarct imaging indicated cell uptake in the peri-infarct zone. Myocardial uptake of labeled cells activity correlated in particular with late gadolinium-enhanced infarct border zone mass (r=0.84, P<0.0001); it also correlated with peak TnI (r=0.76, P<0.001), severely-abnormal/absent perfusion segment number (r=0.45, P=0.008), and late gadolinium-enhanced infarct core (r=0.58, P=0.0003) but not with echocardiography LVEF (r=-0.07, P=0.68) or gated single-photon emission computed tomography LVEF (r=-0.28, P=0.16. The correlation with cardiac magnetic resonance imaging-LVEF was weak (r=−0.38; P=0.04). Conclusions-This largest human study with labeled bone marrow CD34+ cell transcoronary transplantation after recent STsegment-elevation myocardial infarction found that myocardial cell uptake is determined by infarct size rather than LVEF and occurs preferentially in the peri-infarct zone. (Circ Cardiovasc Imaging. 2013;6:320-328.) Key Words: cardiac magnetic resonance imaging ◼ CD34 + cells ◼ gadolinium late-enhancement ◼ infarct border zone ◼ myocardial infarction-cellular therapy ◼ progenitor cell tracking ◼ single-photon emission computed tomography ◼ transcoronary cell transplantation © 2012 American Heart Association, Inc. P rogenitor cell therapy is emerging as a promising therapeutic modality in patients with acute myocardial infarction (MI) and substantial myocardial injury, and over the la...

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Bone marrow stem cell imaging after intracoronary administration

Cited by 46 publications

References 5 publications

Pilot Trial on Determinants of Progenitor Cell Recruitment to the Infarcted Human Myocardium

Pilot Trial on Determinants of Progenitor Cell Recruitment to the Infarcted Human Myocardium

Stem cell therapy for cardiovascular disease: the demise of alchemy and rise of pharmacology

Infarct Size Determines Myocardial Uptake of CD34 ⁺ Cells in the Peri-Infarct Zone

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Bone marrow stem cell imaging after intracoronary administration

Cited by 46 publications

References 5 publications

Pilot Trial on Determinants of Progenitor Cell Recruitment to the Infarcted Human Myocardium

Pilot Trial on Determinants of Progenitor Cell Recruitment to the Infarcted Human Myocardium

Stem cell therapy for cardiovascular disease: the demise of alchemy and rise of pharmacology

Infarct Size Determines Myocardial Uptake of CD34 + Cells in the Peri-Infarct Zone

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Infarct Size Determines Myocardial Uptake of CD34 ⁺ Cells in the Peri-Infarct Zone