Newly Discovered Heart Stem Cells Make Muscle And Bone

The research group of Richard Harvey of the Victor Chang Cardiac Research Institute in Australia has identified a new and relatively abundant pool of stem cells in the heart. This discovery was published in the December issue of Cell Stem Cell and shows that this pool of adult stem cells in the heart have the capacity to grow in culture outside the body and possess the ability to form many different cell types, including muscle, bone, neural and heart cells.

This discovery could lay the foundations for regenerative therapies that enhance tissue repair in the heart. Damaged heart muscle does no usually repair itself, and the incredibly hostile environment within the heart after a heart attack contributes to the wide-scale loss of cells, including stem cells, after a heart attack. According the Richard Harvey, “In the end, we want to know how to preserve the stem cells that are there and to circumvent their loss.”

These newly described cardiac stem cells are found in both developing and adult hearts, and, as in bone marrow and other organs, they are predominantly found in the vicinity of blood vessels. Harvey says despite the ability of these cells to form other cell types (a characteristic known as multipotency), these cells might have a bias toward producing heart-specific tissues. Their flexibility could be a byproduct of the need to remain responsive to the environment and to many types of injury. Harvey’s discovery comes at a time when stem cells harvested from human hearts during surgery are just beginning to show promise for reversing heart attack damage,

While cell-based therapies do have potential for repairing damaged heart tissue, Harvey ultimately favors the notion of regenerative therapies designed to tap into the natural ability of the heart and other organs to repair themselves. There is more work to do to understand exactly what role these stem cells play in that repair process. Harvey’s research team is now exploring some of the factors that bring those cardiac stem cells out of their dormant state in response to injury and protect their stem cell status.

LateTIME Trial Gives More Reason for Optimism Than Originally Thought

A recently completed clinical trial called the “LateTIME” trial examined the ability of bone marrow stem cell transplants into the heart after a heart attack to help heal the heart. While the study showed that such transplants were safe, they failed to show efficacy for this procedure. Nevertheless, the scientists who performed this study have re-examined their data and see reasons for optimism in this procedure.

The results from the LateTIME trial were reported at the 2011 American Heart Association (AHA) Scientific Sessions conference, and were also later published in the Journal of the American Medical Association (JAMA). While patients who received the treatments showed no more improvement than the group that was not injected with their own bone marrow stem cells, JAMA editors believe that these data give some reason for optimism.

First of all, some of the patients in the LateTIME trial showed effective recovery following bone marrow implantations. Furthermore, these patients who showed improvements tended to group with those patients who received their bone marrow treatments earlier rather than later. Therefore, it is possible that bone marrow implantations into the heart are potentially effective if they are given relatively soon after the heart attack.

Already the co-investigators who directed the LateTIME trial (Dan Simon and Marco Costa of UH Case Medical Center), are currently conducting in a similar trial called the “TIME” trial that already has reduced the time between attack and stem cell injection. The research team is optimistic that the time variable adjustment in the new trial will generate favorable outcomes. Dan Simon commented: “We have reason to believe, as supported by data, that an adjusted injection timeframe could yield stronger results and support for stem cell injections rebuilding damaged heart muscle and function.” Dr. Simon is the chief of Cardiovascular Medicine at UH Case Medical Center and the Herman K. Hellerstein Professor of Cardiovascular Research at Case Western Reserve University School of Medicine. Marco Costa sounded an additional optimistic note: “The results were not positive, but if you put it into perspective, the foundation or blueprint for success was discovered and that could certainly lead to advanced treatment options for these patients. Dr. Costa is the Director of the Interventional Cardiovascular Center and Research & Innovation Center at UH Case Medical Center, and also serves as Professor of Medicine at Case Western Reserve University School of Medicine.

Both clinical trials share a theory of heart repair. Namely that specialized stem cells in the bone marrow have the ability to promote blood vessel growth, prevent cell death and transform themselves into a number of tissues, including heart muscle. After an acute heart attack, a remodeling process is initiated in the heart in an attempt to compensate for the damaged areas. It is highly probable that the condition of the heart muscle several weeks after a heart attack differ considerably from the heart muscle in the acute stage setting. In fact, for some patients delaying the delivery of stem cells by two to three weeks may have been better than initiating the treatment during the acute phase.

All patients who participated in the LateTIME study underwent baseline assessments that included medical history, physical exam, electrocardiogram, blood draws, and MRI tests. Participants were then assigned randomly to receive the stem cells or placebo within the previously mentioned two – three-week timeline. The morning of stem cell or placebo infusion, a blood draw and bone marrow aspiration procedure of the hip bone are conducted to collect the stem cells. Later the same day, either stem cells or placebo are then infused through a catheter and directly into the damaged area of the heart. Following the first 24 hours of the infusion, participants wear a small ECG machine, or Holter monitor. Additionally, patients record their body temperature twice a day for 30 days post infusion. Follow up visits at one month, three, six, and twelve and twenty-four months after the procedure, during which baseline assessment tests are conducted. The TIME trial adjusts that variable and results of this trial will be published in two years.