Cardiac muscle regeneration – Myocardial infarction is a major cause of congestive heart failure, leading to high mortality in European populations. Presently, there are no effective restorative therapies to repair the damage and fibrosis incurred by the heart muscle. Injection of exogenous stem cell populations into infarct patients (and animals in controlled experiments) has provided some small but questionable improvement in heart function. The improvement was shown to be a bystander cell effect, as no donor cells contributed to the regeneration of the heart muscle tissue. Rather than stem cell transplantation therapy, Dr. D. ten Berge uses Wnt proteins, a key signaling pathway in stem cells and in tissue regeneration, to promote in vivo stem cell growth and maintenance. In addition to studying the effects of Wnts on maintaining the pluripotency of ES cells and iPS cells, he is studying the effects of Wnt liposomes on embryonic stem cell-derived cardiomyocytes and would like to work with patient-derived iPS cells.

Skeletal muscle stem cells – This focus of research involves study of the fundamental aspects of muscle stem cells and muscle cell differentiation. Satellite cells are the predominant stem cell population in adult muscle and have robust regenerative potential. Of importance for skeletal muscle regeneration or repair is a full knowledge of the muscle cell differentiation hierarchy, the growth factors and local microenvironment that promote the normal development and differentiation of this tissue. Dr. G. Schaaf is isolating and characterizing muscle stem and progenitor cells. His group is investigating a novel muscle stem cell marker that promises not only to be an important reagent in muscle stem cell enrichment, but could also provide insight into the growth factors regulating muscle cell lineage potential. Direct delivery of muscle stem cells in patients holds promise for repair of local tissue damage for example, stress urinary incontinence.
Another research line involving the development of muscle cells from non-muscle cells such as pericytes, holds further promise for quality of life improvements. These collaborative studies include Dr. M. Crisan an EMBO fellow and Dr. E. Dzierzak.

Cancer - Studies of the cancer stem cells responsible for rhabdnomyosarcoma are underway. Dr. G. Schaaf is comparing the normal and malignant muscle cell differentiation hierarchy to determine which cells are responsible for continuous tumor growth. Targeted therapies aimed at genetic/epigenetic factors (collaboration with Prof. Rob Pieters, Kindergeneeskunde) to eliminate the rhabdnomyosarcoma stem cells are anticipated.