Clinical Trial Demonstrating Benefit of Bone Marrow Stem Cells Administered > 3 Months Post Infarction

Frankfurt, Germany

The concept of utilizing bone marrow cells to decrease scar tissue and improve patient prognosis after myocardial infarction has been previously tested clinically in patients. The majority of previous trials involved administration of autologous bone marrow within a certain time frame (usually 2-12 days) after the myocardial infarct. The reason for this is that subsequent to tissue injury there is a release of chemotactic agents by the injured tissue which induces homing of stem cells to the area of injury.

In a study published today (Assmus B, et al, Transcoronary transplantation of progenitor cells after myocardial infarction N Engl J Med. 2006 Sep 21;355(12):1222-32), the efficacy of bone marrow administration in patients who have had the infarct earlier than 3 months before cell therapy was tested. This is a very important clinical experiment since numerous patients do not have access to stem cell therapy in the immediate post-infarct time frame.

The study used 75 patients with stable ischemia which were randomized to receive either no cell infusion (23 patients) or infusion of circulating progenitor cells (24 patients) or bone marrow cells (28 patients) into the patent coronary artery that supplied the most dyskinetic left ventricular area. The patients in the control group were subsequently randomly assigned to receive CPC or BMC, and the patients who initially received BMC or CPC crossed over to receive CPC or BMC, respectively, at 3 months' follow-up.

The investigators noted that the absolute change in left ventricular ejection fraction was significantly greater among patients receiving bone marrow (+2.9 percentage points) than among those receiving circulating progenitor cells (-0.4 percentage point, P=0.003) or no infusion (-1.2 percentage points, P<0.001). Further evidence of stem cell effects were noted by the observation that the increase in global cardiac function was related to significantly enhanced regional contractility in the area targeted by intracoronary infusion of bone marrow cells. Furthermore, when the patients were crossed over the intracoronary infusion of bone marrow was associated with a significant increase in global and regional left ventricular function, regardless of whether patients crossed over from control to bone marrow or from circulating blood cells to bone marrow.

This apparent ability of bone marrow to induce increased heart function, long-term after the infarction has occurred suggests that the beneficial effects of stem cells are not strictly dependent on the chemotactic gradient induced by tissue injury in the 2-12 days post-infarct period.

There are several patents covering the use of bone marrow cells for cardiac regenerative uses. Below are two examples:

US Patent # 7,097,832 issued to Kornowski, et al. on August 29, 2006 entitled “Intramyocardial injection of autologous bone marrow” and assigned to Myocardial Therapeutics, has one independent claim covering “A method of enhancing collateral blood vessel formation in a subject comprising directly administering to sites in heart or limb tissue an effective amount of autologous bone marrow aspirate to induce collateral blood vessel formation in the tissue.”

US Patent # 6,805,860 issued to Alt; Eckhard on October 19, 2004 entitled “Method of transluminal application of myogenic cells for repair or replacement of heart tissue” has several independent claims covering administration of cells for myocardial regeneration. Specifically, claim # 5, which covers:

“A process for repairing tissue of an organ in a patient's body, which comprises delivering cells that have the capability to replace tissue of a failing organ to the site of the tissue to be repaired, by an intraluminal application through a blood vessel of said site, and occluding said blood vessel proximal to the location of cell entry therein via said intraluminal application during at least a portion of the duration of said cell delivery to increase the concentration of delivered cells at said site, wherein said organ is the patient's heart, and said blood vessel leads to the site of heart tissue to be repaired.”

Dependent claim 10 specifically covers bone marrow cells as a useful cellular source.