One group that reported somewhat better results was the CIRM-funded team led by Eduardo Marban at Cedars-Sinai in Los Angeles. They used specialized stem cells taken from the patient’s own hearts that were multiplied in the lab before they were injected back into the patient. He postulated that these cells were closer in character to the heart muscle that was needed than were the bone-marrow or fat-derived mesenchymal stem cells being used by most other teams.
While he was pleased with the result, he wasn’t satisfied. People often talk about the need to take bench research to the bedside, but what is often just as important is taking the clinical findings and going back to the bench to figure out what is producing the clinical result and then use that knowledge to get even better clinical outcomes.
Using an animal model Marban found that that the infused stem cells seem to act in two ways. Through a normal cycling process existing heart cells contribute to the formation of new heart cells throughout our lives and it looks like the infused stem cells turn up that process. The infused cells also act to summons a patient’s existing native heart stem cells and cause them to increase their activity repairing damaged tissue. The group published their work in EMBO Molecular Medicine. A Cedars press release quotes Marban on the dual action:
“We're finding that the effect of stem cell therapy is indirect. It stimulates proliferation of dormant surviving host heart tissue, and it attracts stem cells already in the heart. The resultant new heart muscle is functional and durable, but the transplanted stem cells themselves do not last long.”Marban’s team had one of CIRM’s first round of Disease Team Awards (described here), which helped him perfect a procedure that attracted funding from the National Institutes of Health to conduct an early phase clinical safety trial, which is ongoing. His company, Capricor, also received an award in CIRM’s second round of Disease Teams, which will fund the second phase clinical trial expected to begin later this year. He has already completed one clinical trial using a different procedure and that is the trial that showed the results that led him back to the bench. We've blogged about that clinical trial and other work here.
In the press release Marban also discusses this important step of going back to the lab to figure out how something is working:
"Understanding the cellular sources and mechanisms of heart regeneration is the first step toward refining our strategies to more effectively regenerate healthy tissue after heart attacks.”D.G.
Malliaras K, Zhang Y, Seinfeld J, Galang G, Tseliou E, Cheng K, Sun B, Aminzadeh M, & Marbán E (2012). Cardiomyocyte proliferation and progenitor cell recruitment underlie therapeutic regeneration after myocardial infarction in the adult mouse heart. EMBO molecular medicine PMID: 23255322