Stem Cell Therapy for RV Failure in PAH: Overview and Clinician Interview

In addition to preclinical results, a case report of an infant with hypoplastic left heart syndrome indicated that intracoronary infusion of autologous BM-derived progenitor cells was associated with improved RV function and RVEF.15 A study of 9 children with severe terminal heart failure demonstrated improvement in LVEF and New York Heart Association classification after intracoronary infusion of autologous BM-derived MNC.16

In a phase 1 clinical trial, children with hypoplastic left heart syndrome showed improvements in RVEF and clinical status after intracoronary administration of autologous cardiac progenitor cells compared with patients who underwent palliation surgery without stem cell therapy.17

“Given that administration of stem cells targeting the LV has already been shown to yield clinical benefits, there is ample reason to similarly use stem cells to treat the RV,” the authors concluded. “We hypothesize that reinforcing the RV rather than trying to treat the lungs in PAH could be an alternative approach to increasing patient survival.”

To further explore the topic, Pulmonology Advisor spoke with Reza Ardehali, MD, PhD, associate professor of medicine in the University of California, Los Angeles, Division of Cardiology and a member of the university’s Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research.

Pulmonology Advisor: What does the evidence to date suggest about the potential role of stem cell therapy as a treatment for RV failure in PAH?

Dr Ardehali:The role of stem cells in RV failure and PAH is poorly understood. This is largely [because of] our lack of knowledge regarding differences between RV and LV cardiomyocytes. [Although] the majority of the LV cardiomyocytes are derived from the first heart field progenitors during early embryonic development, the RV cardiomyocytes have their origin in the second heart field.

Traditionally, it has been suggested that at the cellular levels, LV and RV cardiomyocytes are similar, but they are exposed to different pressures and stresses during embryonic and postnatal development that shape their functional characteristics. To realize the potential of stem cell therapy to treat RV failure, it is necessary to generate chamber-specific cardiomyocytes. Therefore, more research is needed to determine the subtle but important cellular differences between RV and LV cardiomyocytes.

Pulmonology Advisor: What are the proposed mechanisms by which this may be an effective treatment strategy?

Dr Ardehali: Transplantation of cardiomyocytes derived from pluripotent stem cells could theoretically replace the damaged myocardium. However, current attempts have shown poor engraftment of the transplanted cells. Furthermore, our inability to generate chamber-specific cardiomyocytes is also a problem with transplantation studies, in which any contamination with nonmyocytes or nodal cells may induce arrhythmia after cell transplantation.

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Pulmonology Advisor: What should be the focus of future research in this area?

Dr Ardehali:Future research should focus on developing strategies to produce chamber-specific cardiomyocytes from pluripotent stem cells. In addition, improving the survival of the transplanted cells and ensuring their structural and functional integration into the host myocardium is a priority.


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