Intracardiac Transplantation of Already Specifically Dedifferentiated Circulating CD34⁺ Cell Subsets Would Favor Post-Ischemic Myocardial Regeneration.

Several groups, mainly from Germany and Japan, have recently conducted different phase-I clinical studies in which autologous bone marrow (BM) mononuclear cells (MNCs) were reinjected either directly in the ischemic area or intra-coronary in patients with severe post-infarct cardiac failure, resulting in a significant improvement of myocardium viability and/or reperfusion. However, besides “true” HSCs, BM-MNCs represent a mixture of mesenchymal progenitor cells, angioblasts, and maybe other progenitor cells, which does not allow to identify the type(s) of cells potentially responsible for improvement. Moreover, the obstructed coronary artery was always repermeabilized, which biases the evaluation of posttransplant myocardial reperfusion. We have personally chosen an other original approach using mobilized and purified circulating CD34⁺ cells. We and others have indeed demonstrated that mobilized CD34+cells were in fact subdivided into various subsets: of course, the most important (~75%) is the truly hematopoietic subset (CD34⁺/133⁺), of which a CD38⁻ part is probably close to the very primitive HSC. But other smaller subsets are immunophenotypically characterized either as mature (CD34⁺/VEGFR-2⁺) or immature (CD34⁺/133⁺/VEGFR-2⁺) endothelial progenitor cells - thus potentially capable of neoangiogenesis -, or as muscle progenitors (Desmin⁺) and even more as cardiomyocytes (Troponin-T⁺). In a phase-I trial benefiting of the approval of the regional ethical committee, patients suffering of post-infarct cardiac failure are selected according to the following criteria: left ventricular ejection-fraction (LVEF) =35%; distinct area of left ventricular-wall akinesis determined by PetScan; candidates for coronary artery by-pass grafting (CABG), but without any repermeabilization of the coronary artery involved in the infarction; age =70 y. After a 6-days mobilization by G-CSF, circulating CD34+ cells are collected, then purified by immunomagnetism and immediately reinjected at d+7 during CABG, all around and within the infarcted area. The first evaluable patients well tolerated cell mobilization - and collection phases, as well as operative and post-operative periods. Three patients have presently a follow-up = 1 y post-transplantation. Two show a striking gain in LVEF (14 and 20% respectively) with an important improvement in myocardium viability, reperfusion and contractility, and finally in exercise capacity (from class IV to class I in New-York Association functional class). Although very encouraging, these results have to be confirmed in further patients.