Planta Med 2015; 81 - PW_61
DOI: 10.1055/s-0035-1565685

Crataegus ssp. promotes late-stage cardiac differentiation and regeneration

J Halver 1, CC García 1, E Willems 2, D Schade 1
  • 1Department of Chemistry and Chemical Biology, TU Dortmund University, Dortmund, Germany
  • 2Sanford-Burnham Medical Research Institute, La Jolla, United States

The minimal and clearly insufficient ability of the adult heart to regenerate after ischemic injury is a great appeal for identifying biological mechanisms, substances and factors that improve this process [1]. Two main sources for cardiomyocyte renewal and regeneration have emerged in the field: a) adult multipotent progenitor cells and b) pre-existing cardiomyocytes [2].

Based on the many positive effects on the myocardium after infarction and the overall cardiovascular protective activity of Crataegus ssp. (extract WS®1442) [3], we aimed at studying whether also mechanisms of cardiac differentiation and regeneration could possibly play a role.

Here, we show that WS®1442 efficiently stimulated cardiomyocyte differentiation from murine and human ESCs in a dose-dependent manner after mesoderm was formed. This activity was thoroughly validated in a mESC-based (CGR8-Myh6-GFP) spontaneous differentiation assay. First bioassay-guided fractionations of the extract suggested that this activity is reserved for specific compound classes.

According to the observed activity profile, we hypothesize that the identified active fractions in WS®1442 could possibly target multipotent progenitors, stimulate their differentiation towards the cardiac lineage but also expand their pool. Further elucidation of the underlying cellular and molecular mechanisms might lead to novel targets that can be exploited for ex vivo expansion of cardiac progenitor cells. Eventually, it will be interesting to see whether (and how) our in vitro findings translate to in vivo regeneration.

References:

[1] Schade D, Plowright AT. Medicinal Chemistry Approaches to Heart Regeneration. J Med Chem 2015, in press

[2] Harvey RP, Graham RM, Pu WT. Heart Regeneration and Rejuvenation. Stem Cell Res 2014; 13: 521 – 714

[3] Koch E, Malek FA. Standardized extracts from hawthorn leaves and flowers in the treatment of cardiovascular disorders – preclinical and clinical studies. Planta Med 2011; 77: 1123 – 1128