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Institute for Regenerative Medicine • IREM

Pluripotent Cells and iPSC Core

Research Focus

Melanie Generali, PhD

In 2019 an estimated 17.9 million people died from cardiovascular disease, representing 31% of all global deaths. Insufficient blood flow based on narrowing or occlusion of coronary arteries can lead to tissue necrosis. There is an urgent need for reperfusion of the ischemic heart tissue to avoid cardiac cell death and necrosis or afterwards remuscularization in case of cell death, respectively.

Tissue engineering is a discipline with the intention to repair, replace or regenerate injured tissues. The three key components are i) cells, ii) starter material, and iii) biological / mechanical stimuli. A promising cell source in regenerative medicine is human induced pluripotent stem cells (iPSC). These cells are established by introducing several factors to somatic cells and then can differentiate into any cell type of the human body. the cells of a various tissues or organs (pluripotency) and grow indefinitely (proliferation).

One the one hand, we investigate the use of tissue engineered vascular grafts (TEVG), where we have optimized the scaffold matrices and cell sources for cardiovascular tissue engineering in order to prevent thrombosis and improve mechanical properties of small tissue engineered vascular grafts. We have generated iPSC based on peripheral blood nuclear cells and differentiated them into smooth muscle cells as well as endothelial cells. Resulting TEVG contained an αSMA-positive layer in the interstitium and a thin luminal layer of vWF-positive cells.

On the other hand, we aim to treat myocardial infarction by using iPSC-derived cardiomyocytes. These cells are purified and produced under xenofree conditions and in accordance with good manufacturing practice (GMP)-compliant guidelines. This is a collaborative project with the Center for iPS Cell Research and Application (CiRA), Kyoto University. In a next step, we we aim to specifically functionalize and target these cells towards the specific ischemic environment of myocardial infarction for next generation cell-based therapies

Besides of our research activities, I have initiated and established a new iPSC Core Facility (iPSCore) at the UZH to offer expertise, instrumentation and support in the area of iPSC to all researchers. The mission of iPSCore is to support basic and translational research by facilitating all aspects of iPSC technology including the derivation, differentiation and distribution of human iPSC lines. iPSC Core Facilities

Group Members

PostDoc
Affef Abidi

Technician
Darcie Jackson
Debora Meier
Dennis Zorndt