CHARACTERIZATION AND ENERGETIC METABOLISM ANALYSIS OF DIFFERENT POPULATIONS OF UMBILICAL CORD MESENCHYMAL STEM CELLS FOR THE TREATMENT OF STROKE

Stroke is a leading cause of death and disability worldwide. A direct consequence of oxygen and glucose deprivation during stroke is the dysfunction of mitochondria that impairs oxidative metabolism and contributes to oxidative stress, neuronal death and inflammation. Human umbilical cord (UC)-derived MSCs (UC-MSCs) are an attractive source for regenerative medicine purposes due to their self-renewal and multipotent differentiation potential, immunomodulatory and anti-inflammatory abilities. Notably, because UC is supplied from only three blood vessels, the UC-MSCs are physiologically adapted to survive in a relatively hypoxic and glucose poor environment leading to the hypothesis that these cells may have a beneficial potential for the treatment of ischemic pathologies, such as stroke. However, it is still unclear whether MSCs from a certain compartment of UC are therapeutically superior to MSCs from other compartments. The aim of this PhD research project is to characterize the human UC-MSCs based on their neuroprotective, trophic, and immunomodulatory capacities, as well as test their energetic metabolism potential for the treatment of ischemic stroke. In summary, proteomic analyses of UC-MSCs – including 2D-SDS-PAGE, 2D Western blot and mass spectrometry analysis – showed the expression of novel anti-inflammatory, neuro- and angioprotective as well as anti-oxidative and hypoxia response markers, making them a promising cellular source for stem cell-based treatment of central nervous system diseases, including stroke. In addition, live-cell metabolic assays with the Seahorse technology showed that all three types of UC-MSC populations – perivascular (PV), Wharton’s jelly (WJ) and cord lining (CL) MSCs – have an elevated capacity of survival and adaption to OGD/R conditions due to their energetic metabolism and mitochondrial function. This finding suggests that all three types of UC-MSCs could be an effective source of healthy mitochondria for stem cell-based therapy in ischemic diseases.