The clinical use of immunoselected CD34+ stem cells has been assessed in a Proof of Concept trial financed by the French Health Ministry and the AFSSAPS 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 Laboratory. The injection of the graft cells was performed directly into the myocardial lesions within 24 hours after sampling during the coronary bypass surgery.
In addition to the feasibility and the perfect tolerability of the graft cell injection, the clinical benefit observed up to a mean follow-up period of 53 months are exceptional. Tissue regeneration as well as tissue revascularization within scar tissue were clearly documented by PET Scan.
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 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 into the study were having 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.
In order to provide some comparison with existing treatments stenting or coronary bypass surgery would lead to an increase in LVEF up to 5 to 7 points. These treatments have a limited impact of the life expectancy after sever AMI and do not induce any form of regeneration of cardiac tissue
Most of the treated patients with cell graft experience a nearly normal life with for some of them a follow-up period exceeding now 6 years.
None of the three patients requiring initially a heart transplant is any longer awaiting such therapy with the additional advantage of not necessitating immunosuppressive therapy as the cell graft received were 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.
This treatment has the true potential to become a leading treatment for severe damage to the heart due to its ability to satisfy, at least in part, an unmet need for more effective and/or more affordable therapies for severe AMI and prevention of the resulting CHF.
“Long-term benefit of intracardiac delivery of autologous granulocyte–colony stimulating factor-mobilized blood CD34+ cells containing cardiac progenitors on regional heart structure and function after myocardial infarct” Pasquet S , Sovalat H , Hénon Ph , et al. Cytotherapy, vol. 11, N°8, December 2009, 1002-15