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

Abstract

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.

SDF-1 in myocardial repair

“…We further hypothesized that the benefit would be observed in the absence of stem cell infusion as there is constitutive stem cell release from the bone marrow that appears to be not only increased after AMI, 14 but the stem cells appear to be more responsive to SDF-1 signaling. 15,16 Previous studies from our laboratory demonstrated that delivery of a nonviral DNA plasmid engineered to express SDF-1 resulted in cardiac benefit. 4 This plasmid is named JVS-100.…”

Imaging Cardiac Stem Cell Transplantation Using Radionuclide Labeling Techniques: Clinical Applications and Future Directions

“…20 significantly lower stem cell retention (average of 2.5%) was found in a subgroup of patients with chronic Mi. several other studies with smaller patient numbers, such as Blocklet et al and Caveliers et al, also demonstrated comparable stem cell retention rates.…”

Stem Cell Therapy in Myocardial Infarction Clinical Point of View and the Results of the REANIMA Study (REgenerAtion of Myocardium with boNe Marrow Mononuclear Cells in MyocArdial Infarction)

“…On the other hand, a direct intramyocardial injection of stem cells in patients with CMI seems to be preferred mode of cell delivery. Some animal model and pilot human trial confirm this assumption (Hou et al, 2005;Schächinger et al, 2008). Our results have shown b e n e f i t o f b o n e m a r r o w d e r i v e d s t e m c e l l s g i v e n i n t o t h e m y o c a r d i u m d u r i n g C A B G improving LVEF and myocardial perfusion which is in accordance with other studies of bone marrow derived stem cell therapy with CABG (Donndorf et al, 2011).…”

“…Those areas need revitalization with stem cells, but the question is whether the same cells are needed for the chronic IM as for the acute MI, and whether the same route of delivery would be equally efficient? Very interested human pilot study of tracking the labeled circulating progenitor cells ( myocardium decreased progressively over the time (Schächinger et al, 2008) alludes the answer on the second question. Human trials comparing bone marrow derived MNC and peripheral blood progenitor cells (PBPC) exist at least for AMI patients with inconclusive and contradictory results on their regenerative capacity (Schächinger et al, 2004;Hirsch et al, 2010).…”