Just as no two people are the same, neither are the cells in their bone marrow, the most common source of stem cells in clinical trials trying to repair damage after a heart attack. Doris Taylor of the Texas Heart Institute in Houston, which is just a couple hours drive from the site of this year’s World Stem Cell Summit in San Antonio, gave a key note address this morning that offered some good reasons for the variable and often disappointing results in those trials, as well as some ways to improve on those results.
The cells given in a transplant derived from the patient’s own bone marrow contain just a few percent stem cells and a mix of adult cells, but for both the stem and adult cells the mix is highly variable. Taylor said that in essence we are giving each patient a different drug. She discussed a series of early clinical trials in which cell samples from each patient were banked at the National Heart and Lung and Blood Institute. There they could do genetic and other analysis on the cells and compare that data with how each individual patient faired.
In looking at the few patients in each trial that did better on any one of three measures of improved heart function, they were indeed able to find certain markers that predicted better outcome. In particular they looked at “triple responders,” those who improved in all three measures of heart function. They found there were both certain types of adult cells and certain types of stem cells that seemed to result in improved heart health.
They also found that two of the strongest predictors were gender and age. Women generally develop degenerative diseases of aging like heart disease at an older age than men and since many consider aging to be a failure of our adult stem cells, it would make sense that women have healthier stem cells.
Taylor went on to discuss ways to use this knowledge to improve therapy outcomes. One way would be to select for the more potent cells identified in the NHLBI analysis. She mentioned a couple trials that did show better outcomes using cells derived from heart tissue. One of those is work that CIRM funds at Cedars-Sinai in Los Angeles.
Another option is replace the whole heart and she closed with a review of what is probably her best-known work, trying to just that. In rats and pigs, she has taken donor hearts and used soap-like solutions to wash away the living cells so that all that is left behind are the proteins and sugars that make of the matrix between cells. She then repopulates the scaffolds that still have the outlines of the chambers of the heart and the blood vessels that feed them, with cells from the recipient animal. She has achieved partially functional organs but not fully functional ones. She—along with other teams around the world—is working on the remaining hurdles to get a heart suitable for transplant.