A new clinical trial to test how a high dose of stem cells delivered via a method called retrograde coronary sinus infusion affects end stage heart failure patients is showing promising results. The method involves delivering the cells backwards through the heart through the coronary sinus.
“We performed this technique because the veins do not have diseases like the arteries of the heart and it allows the cells to ‘marinate’ the entire heart at once,” explains lead investigator Amit N Patel, director of cardiovascular regenerative medicine at the University of Utah School of Medicine, Salt Lake City, USA. The international team of researchers’ work appears in Stem Cells Translational Medicine.
Patients with advanced heart failure currently have few treatment options, mainly heart transplantation or ventricular assist devices. In the search for new and effective treatments, biological-based cell and gene therapies are potential solutions. They use the body’s own native repair mechanisms—in particular, stem cells—to reverse or restore function in damaged organs, tissue and blood vessels.
These stem cells can come from sources such as umbilical cord, adult fat, skin tissue and more. The most widely used source of cells when treating cardiovascular disease is the patient’s own bone marrow. This is because it contains the specialised stem cells that go on to become blood cells, and because bone marrow is home to mesenchymal stem cells (MSCs), which are adult stem cells that can differentiate a variety of cells types depending on the conditions of the culture they are grown in.
The method for delivering the cells to their proper cellular targets is also an important variable affecting the success of biological-based therapy. In this study, the authors’ goal was to evaluate how retrograde bone marrow cell delivery might impact patients with either ischaemic or non-ischaemic heart failure.
Patel explains, “Methods such as direct injection during open heart surgery or via catheter have shown some success, but the problem is that with these methods you can only safely deliver a limited number of cells and they do not always migrate to the areas that need repair. This makes the translation from pre-clinical models to human dosing more challenging.”
“Our previous pilot studies on patients with non-end-stage heart disease indicate that retrograde delivery into the coronary sinus by infusion is successful, as it gives doctors the ability to deliver large numbers of stem cells directly to the impacted areas with minimal side effects to the patient.” The coronary sinus is accessed via the right femoral vein using a balloon infusion catheter.
However, this method had never before been tested on patients suffering from advanced heart failure. That is what the team’s study wanted to determine. “It is the first clinical trial to use a large dose of nucleated bone marrow cells infused into the coronary sinus of heart failure patients,” he says.
Over the course of the 12-month trial, 60 patients were divided into two test groups according to whether they had experienced an ischaemic or non-ischaemic cardiac incident. Twenty-four patients in each group were given the bone marrow infusions (the BMAC groups), while the other six patients in each comprised the control group and received standard heart failure care. Patients in the BMAC groups were taken to the catheterisation laboratory where both the harvest of bone marrow and infusion of cells occurred during the same visit. Patients returned for follow-up visits at one, three, six and 12 months.
“At the end of the trial, our tests revealed that all patients receiving the bone marrow infusions had improved heart function, with no adverse side effects, especially those in the non-ischaemic group,” Patel reports. “As a result, we believe that this study provides the basis for a larger clinical trial in advanced heart failure patients.”
“The results of this study to infuse a patient’s own stem cells into the coronary sinus, a large vessel that forms a partial circle around the heart, are promising and suggest the need for further investigation,” says Anthony Atala, editor-in-chief of Stem Cells Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine, Winston-Salem, USA.