The hunt for cardiomyocyte precursors for the treatment of heart failure: GFRA2 marks the spot

Written by Adam Price-Evans

Researchers from Osaka University (Osaka, Japan) have identified a surface marker that is vital for cardiac development and can be used to isolate and study human cardiac progenitors, which may help researchers develop a regenerative or cell replacement therapy for heart failure

The transplantation of cardiomyocytes derived from stem cell sources is an attractive route for the treatment of heart failure. A major hurdle has been the lack of specific markers for cardiac progenitor (CP) cells, making their identification and isolation for research or therapeutic use difficult. Researchers from Osaka University (Osaka, Japan) have discovered a molecular surface marker specific to cardiomyocyte precursors, GFRA2, allowing their isolation and therefore their study and potential transplantation for conditions such as heart failure.

The team demonstrated that the glycosylphosphatidylinositol-anchor containing neurotrophic factor receptor Gfra2, specifically marks CP cells in the first and second heart field in mice and humans.

The utilization of the GFRA2 marker facilitated the accurate isolation of stage-specific CPs with high purity. Gfra2 mutants also implicated GFRA2 in cardiomyocyte differentiation and development both in vitro and in vivo, thus highlighting its importance in heart development.

Additionally, abnormal function of GFRA2 in genetically engineered mice resulted in noncompaction cardiomyopathy, which is associated with severe heart failure with poor prognosis. This discovery provides important information about this poorly understood disease.

Collectively, the findings highlight the potential of GFRA2 in the investigation and isolation of CPs and the prospect of CP transplantation for the treatment of heart failure in the future.

“Next, we will aim to completely validate the safety of cardiac progenitors isolated with GFRA2, and develop a method to use them most effectively to treat heart failure. We think our study is now about to enter an exciting stage,” concluded author Kenta Yashiro (Queen Mary University of London, UK).

— Written by Adam Price-Evans

Sources: Ishida H, Saba R, Kokkinopoulos I et al. GFRA2 identifies cardiac progenitors and mediates cardiomyocyte differentiation in a RET-independent signaling pathway. Cell Rep. 16(4), 1026—1038 (2016);