The clinical use of immunoselected CD34+ stem cells has been assessed in a Proof of Concept trial to evaluate their regenerative capacity in patients suffering from severe AMI. Seven patients have been included into the program initiated in January 2003. The life expectancy of these patients was lower than 3 years due to the severity of their infarct. Three of the patients were candidate for heart transplant at the time of their inclusion.
Following their informed consent, each patient was administered GCSF for 6 days before collecting by leukapheresis their blood stem cells which were then immunoselected in the Cell Therapy Center. The injection of the graft cells was performed directly into the myocardial lesions within 24 hours after sampling during a coronary bypass surgery.
In addition to the feasibility and the perfect tolerability of the graft cell injection, the clinical benefit shows tissue regeneration as well as tissue revascularization within scar tissue which was clearly documented by PET Scan.
After recent AMI
6 months after stem cells grafting
Such imaging technique using labeled products like glucose and ammonium allow the quantification of functional recovery (regeneration of myocardial tissue) and also the revascularization of myocardium after cell graft.
The necrotic area after AMI does not fixed glucose or ammonium and therefore is not any longer visualized providing a lacuna image on the PET Scan. When the myocardium has initiated its regeneration it become again visualized by fixing labeled ammonium and glucose.
From a clinical standpoint, the myocardial regeneration translated into a progressive improvement of the infarcted zone contractility leading to a parallel improvement of the global cardiac function as illustrated by a reduction of the observed cardiac dilatation and a concomitant significant increase in the left ventricular ejection fraction (LVEF). The LVEF corresponds to the ratio between the systolic ejection volume (ventricular volume when emptied after myocardium contraction) and the diastolic volume (full volume). This a key measure to assess the cardiac muscle function.
For a normal subject LVEF is over 70%. The patients included in the study had a LVEF lower than 35%, clearly indicating the presence of a severe heart failure.
The measurements of the LVEF after cell graft revealed a progressive and prolonged significant improvement up to +43 points (an 160% increase) compared to the pretreatment assessments
Most of the treated patients with cell graft experience a nearly normal life with for some of them a follow-up period exceeding now 13 years.
None of the three patients initially awaiting a heart transplant is any longer requiring such therapy, and, with the additional benefit of no immunosuppressive therapy as the cell graft was prepared from their own cells (autologous stem cells).
Although a number of therapies have proven to improve the cardiac function of a damaged heart, no currently available treatment with the exception of CellProthera has demonstrated an ability to generate myocardial tissue within the scarred regions of a heart underlying the truly innovative character of its therapeutic approach.