On Monday – and appropriately perhaps just in time for St. Valentine’s day – a team of scientists at the Cedars Sinai Heart Institute led by Dr. Eduardo Marbán announced that in a small clinical trial they had repaired damaged heart tissue using an infusion stem cells derived from the heart attack patient’s own heart. The stem cells used- known as Cardiosphere Derived Cells (CDCs) were obtained from a small population of cells isolated from biopsied heart tissue that spontaneously form clusters known as cardiospheres in culture, and have the potential to differentiate into a variety of cardiac cell types.
It’s important to note that the main purpose of this trial was to demonstrate that the technique is safe enough for larger clinical trials, so the significant reduction in scarring and increase in the muscle volume is an impressive result. As yet they have not been able to demonstrate that this improved healing is associated with improved heart function, a question that will need to be addressed in larger clinical trials with longer-term follow up of patients.
In the press release issued by the Cedars-Sinai Heart Institute Dr. Marbán notes that “The effects are substantial, and surprisingly larger in humans than they were in animal tests.”, which is true, though in the pre-clinical research that led to this clinical trial Dr. Marbán and colleagues demonstrated that CDCs are able to promote tissue repair and improve cardiac function in several animal models.
Among several papers reporting on this work, two stand out as particularly important. The first was published in 2007 (1) when Dr. Marbán’s team reported that transplanted human CDCs reduced scarring, increased heart tissue volume and improved cardiac function compared to controls when injected into the damaged areas of mouse hearts following induction of a heart attack. They followed-up this study with another to determine the safety and effectiveness of this technique in a large animal model, as well as refining their infusion technique. In this study, published in 2009 (2), they demonstrated that infusion of autologous CDCs – stem cells derived from the same individual later treated – could safely promote tissue repair and functional improvement in pigs following an induced heart attack. While the reduction in scarring and the amount of new tissue seen in these studies (and in several other studies by this and other research groups) was not quite as large as that seen in the human clinical trial earlier this week, it was certainly significant enough to convince them that this approach should be evaluated in a clinical trial.
It’s worth noting how quickly this field has progressed, as CDCs were first isolated by a team at La Sapienza University in Rome as recently as 2004. In a paper published in that year Professor Alessandro Giacomello and colleagues reported the isolation and characterization of CDCs from mice and humans, and demonstrated that they could survive when injected into mice and differentiate into a range of cardiac cell types, as well as providing the first evidence that CDCs could help repair tissue following a heart attack.
While we will have to wait for further clinical trials before we can know just how beneficial this therapy will be, there’s no denying that it is an exciting development, and one that has only got this far thanks to animal research. And it’s worth remembering that this is only one of numerous innovative approaches being examined as medical researchers seek to mend broken hearts.
1) Smith RR, Barile L, Cho HC, Leppo MK, Hare JM, Messina E, Giacomello A, Abraham MR, Marbán E. “Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens.” Circulation. 2007 Feb 20;115(7):896-908. PubMed: 17283259
2) Johnston PV, Sasano T, Mills K, Evers R, Lee ST, Smith RR, Lardo AC, Lai S, Steenbergen C, Gerstenblith G, Lange R, Marbán E. “Engraftment, differentiation, and functional benefits of autologous cardiosphere-derived cells in porcine ischemic cardiomyopathy.” Circulation. 2009 Sep 22;120(12):1075-83. PubMed:19738142
3) Messina E, De Angelis L, Frati G, Morrone S, Chimenti S, Fiordaliso F, Salio M, Battaglia M, Latronico MV, Coletta M, Vivarelli E, Frati L, Cossu G, Giacomello A.”Isolation and expansion of adult cardiac stem cells from human and murine heart.” Circ Res. 2004 Oct 29;95(9):911-21. PubMed:15472116