Cellular communication in cardiac regeneration

Maring, J.A. (2019)

Doctoral Thesis

Myocardial infarction results in a permanent loss of function in the heart. Currently, there is no therapy available that addresses the heart of the problem: the loss of cardiomyocytes. Cell transplantation has been a focus of cardiac regenerative studies. Interestingly, cell transplantation has effect on cardiac function and vessel formation in the absence of cardiac differentiation, suggesting a role for the paracrine factors. Besides replacing cardiomyocytes, restoring blood flow to the infarcted area is vital. We showed that vasculogenesis is not hampered by the loss of endoglin, but angiogenesis, and network formation was impaired with reduced endoglin expression. We also studied the effect of extracellular vesicles (EVs) secreted by mesenchymal stromal cells (MSC) and cardiac progenitor cells (CPC) on angiogenesis and infarct size. Both in vitro and in vivo angiogenesis was significantly improved in the presence of these EVs. Knockdown of the pro-angiogenic factor EMMPRIN resulted in a reduction in angiogenesis. Injection of the CPC derived EVs into the heart after MI resulted in a decrease in infarct size. Furthermore, total proliferation was increase in the border zone and infarcted area as seen by an increase in Ki67 and Yap. These results show therapeutic potential of EVs for cardiac regeneration.

• Extracellular Vesicles
• Angiogenesis
• Cardiac regeneration
• Cardiac Progenitor Cells
• Endoglin

• All authors: Maring, J.A.
• Supervisor: Goumans, M.J.
• Co-supervisor: Sluijter, J.P.G.; Smits, A.M.
• Committee: Hoeben, R.C.; Atsma, D.E.; Bouten, C.V.C.; Schiffelers, R.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2019-06-12
• ISBN (print): 9789463235075