Planta Med 2015; 81 - SL2B_03
DOI: 10.1055/s-0035-1565303

A phytomedicine approach to stem cell modulation for heart regeneration

D Schade 1
  • 1TU Dortmund University, Department of Chemistry and Chemical Biology, Dortmund, Germany

There is a great medical need for innovative therapies of heart disease that ask for paradigm shifts in pharmacotherapy. In this regard, the low and insufficient ability of the adult human heart to regenerate after myocardial infarction represents a great opportunity to identify chemical modalities, biological factors and mechanisms that improve this process. Owing to milestone discoveries in stem cell biology and regenerative medicine, several attractive technologies and molecules have emerged [1,2].

Based on the protective activity of Crataegus ssp. on the cardiovascular system and its positive effects on the myocardium after ischemic injury [3], we questioned whether mechanisms of cardiac regeneration could also contribute to the pharmacological profile of hawthorn extracts.

We have established a platform of murine and human stem cell-based phenotypic assays to probe differentiation and proliferation of cardiomyocytes (and progenitors). Using an array of readouts, including high-content fluorescence microscopy, flow cytometry and RT-qPCR, we found and validated that extract WS®1442 efficiently stimulated cardiomyocyte differentiation from murine (and human) stem cells in a dose-dependent manner after mesoderm was formed. First bioassay-guided fractionations of the extract suggested that this activity is reserved for specific compound classes.

We hypothesize that distinct Crataegus ingredients target multipotent progenitors, stimulate their differentiation towards the cardiac lineage but also expand their pool, thus addressing one of the mainly discussed potential sources for endogenous heart regeneration. Future studies will have to identify the active ingredient(s) and decipher the underlying cellular and molecular mechanisms which may reveal novel, potentially druggable targets for in vivo heart regeneration.

References:

[1] Längle D et al. ACS Chem Bio>2014; 57

[2] Schade D, Plowright AT J Med Chem 2015, submitted

[3] Koch E, Malek FA Plant Med 2011; 1123