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23-05-2012 | Cardiology | Article

Stem cells show promise for heart failure

Abstract

Free abstract

MedWire News: In the first study of its kind, researchers have succeeded in taking skin cells from heart failure (HF) patients that can differentiate into cardiomyocytes and integrate with cardiac tissue.

The research, published in the European Heart Journal, hints that it could soon be possible to treat the damaged hearts of HF patients with their own human-induced pluripotent stem cells (hiPSCs).

"What is new and exciting about our research is that we have shown that it's possible to take skin cells from an elderly patient with advanced HF and end up with his own beating cells in a laboratory dish that are healthy and young ‑ the equivalent to the stage of his heart cells when he was just born," commented lead author Lior Gepstein (Technion-Israel Institute of Technology and Rambam Medical Center, Haifa, Israel) in a press statement.

Gepstein and team took dermal fibroblasts from two male HF patients (aged 51 and 61 years) and reprogrammed them by retroviral delivery of three transcription factors: Oct4, Sox2, and Klf4.

They also used an alternative strategy to deliver the transcription factors to the skin cells, by way of an excisable polycistronic lentiviral vector, which was capable of being removed afterwards to avoid insertional oncogenesis.

The resulting hiPSCs differentiated into cardiomyocytes that had the same efficiency as control hiPSCs derived from human foreskin fibroblasts, and whose phenotype was confirmed by gene expression and immunostaining studies.

Multi-electrode array recordings revealed the development of a functional cardiac syncytium and adequate chronotropic responses to adrenergic and cholinergic stimulation.

Co-culture studies revealed that functional integration and synchronized electric activities were demonstrated between hiPSC cardiomyocytes and neonatal rat cardiomyocytes. "The tissue was behaving like a tiny microscopic cardiac tissue comprised of approximately 1000 cells in each beating area," Gepstein remarked.

Finally, in vitro transplantation studies in the rat heart demonstrated the ability of the HF-hiPSC cardiomyocytes to engraft, survive, and structurally integrate with the host cardiomyocytes.

"We hope that hiPSCs derived cardiomyocytes will not be rejected following transplantation into the same patients from which they were derived," said Gepstein. "Whether this will be the case or not is the focus of active investigation.

"One of the obstacles in dealing with this issue is that, at this stage, we can only transplant human cells into animal models and so we have to treat the animals with immunosuppressive drugs so the cells won't be rejected."

Gabor Foldes, a Research Associate at the National Heart and Lung Institute at Imperial College London, UK commented: "In addition there are other important aspects one should think of that are not fully addressed… these are the diversity of heart muscle cells (ventricular, atrial, or pacemaker/conductive ones); lack of mature forms of heart muscle cells when grown in a culture dish; [and] lack of clinical grade culture conditions [amongst others].

"So although this is still early days in cardiac cell therapy, results from this study can be a useful addition to further develop heart regeneration strategies."

Gepstein said that if all the limitations of the study are overcome, the process will take at least 5‑10 years to reach clinical trials.

By Piriya Mahendra

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