Intracoronary injection of haematopoietic precursor cells regenerates the borders, but not the core, of old myocardial scars

Abstract

Aims: Cell therapy regenerative potential is hindered by cell access to the infarct zone. We studied function recovery at the scar zone and its impact in global left ventricular function after intracoronary injection of haematopoietic precursor cells. Methods and results: Haematopoietic precursor cells were obtained by blood apheresis in patients with an old myocardial infarction, and the presence of CD34+ and CD133+ cells was quantified. Left ventricular function, volumes, and infarct zone segmental motion were measured by magnetic resonance imaging (MRI) and echo left ventricular segmental strain (LVSS). The aphaeresis product was administered to 20 patients in the coronary artery responsible for the myocardial infarction. High cell yield in blood aphaeresis product allowed us to inject a high number of cells in most patients. Three patients were excluded because of insufficient CD133+ cell number, and one more patient was excluded because of artefacts in MRI images. The remaining 16 patients were compared with 16 controls. After 1 year, infarct zone reduction was related to the number of CD133+ (R = 0.53; P %3C 0.05) and CD34+ (R = 0.63; P %3C 0.01) cells injected. The number of CD133+ cells injected was also related to an improvement in LVSS (R = 0.62; P %3C 0.01). In turn, scar zone reduction was related to an improvement in LVSS (R = 0.64; P %3C 0.01). End-diastolic volume showed a reduction at follow-up in the treated group when compared with control patients. MRI infarct area segments systolic thickness increase improved after treatment in treated patients [expressed as median (interquartile range)] [0.42 (−0.38 to 1.14) vs. 1.06 (−0.10 to 2.12) mm; P %3C 0.01], but not in controls [2.02 (0.75 to 3.4) vs. 1.91 (0.77–3.17) mm; P = not significant (n.s.)]. In cell therapy patients, the borders of the infarct zone, but not the core, showed a significant recovery [proximal rim: 0.48 (−0.18 to 1.33) vs. 1.07 (0.22–2.40) mm; P %3C 0.05, distal rim: 0.75 (0.26–1.40) vs. 1.76 (0.65–2.86) mm; P %3C 0.05, and core: 0.36 (−0.33 to 1.20) vs. 0.60 (−0.18 to 1.62) mm; P = n.s.]. That improvement was not observed in the control group [proximal rim: 1.20 (0.33–2.53) vs. 0.82 (−0.13 to 1.65) mm; P = n.s., distal rim: 1.24 (0.80–1.72) vs. 0.96 (0.19–1.81) mm; P = n.s., and core: 0.30 (−0.42 to 1.64) vs. 0.07 (−0.60 to 1.20) mm; P = n.s.]. Only small size infarcts showed a complete recovery in the cell therapy patients [systolic thickness increase post-treatment increment in infarcts ≤6 segments vs. '6 segments affected: 0.28 (−0.19 to 0.71) vs. −1.21 (−2.60 to −0.53) mm; P %3C 0.01]. Conclusions: Intracoronary injection of peripheral blood-derived haematopoietic precursor cells produces a complete recovery of the borders and partial regeneration of the infarct core, which is directly related to the number of CD133+ and CD34+ cells injected. Cell therapy infarct zone regeneration prevents ventricular remodelling by preserving segmental contractility and halting left ventricular dilatation.