Joseph Itskovitz-Eldor, MD, DSc

Development of Platform Technologies and Protocols for Directed Differentiation of Human Embryonic Stem Cells

Human embryonic stem cells are cells that are capable of differentiating and turning into representative cells of all three germ layers of the embryo and generate each and every tissue of the human body. This unique quality underlies our research focus. By optimizing and controlling the cell's growth parameters, we not only gain a better understanding of early normal and abnormal developmental events, but are also able to direct the cells to commit to any of our desired cell types.

Our two main research focuses are (1) developing platform technologies for the culture and scale-up of human embryonic stem cells, and (2) developing protocols for the directed differentiation of human embryonic stem cells.

1. Development of platform technologies:

(i) Methods and protocols for the culture of undifferentiated human embryonic stem cells in animal-, serum- and feeder-layer free conditions.

(ii) Derivation of new human embryonic stem cell lines in animal- and feeder-layer-free culture conditions under good laboratory practice (GLP). 

(iii) Characterization of the existing human embryonic stem cells using genomics and proteomics methods to increase knowledge of the features of these lines.

(iv) Expansion of differentiating embryonic stem cells in dynamic cell culture (bioreactors).

(v) Growth and differentiation of human embryonic stem cells in 3D structures as a base for tissue engineering.        

2. Development of protocols for directed differentiation:

(i) Differentiation into cardiovascular lineages

(ii) Differentiation into connective tissue progenitor cells

Figure 1:

Sprouting from differentiated human embryonic stem cells. Differentiated cells were allowed to aggregate for 24 hours in medium that is supplemented with human vascular endothelial growth factor165, and then seeded onto type-I collagen or Matrigel in the same medium.

Representative Publications

Sedan, O., Dolnikov, K., Zeevi-Levin, N., Leibovich, N., Amit, M., Itskovitz-Eldor, J., Binah, O. 2008. 1,4,5-Inositol trisphosphate-operated intracellular Ca2+ stores and angiotensin-II/endothelin-1 signaling pathway are functional in human embryonic stem cell-derived cardiomyocytes. Stem Cells 26, 3130-3138.

Yirme, G., Amit, M., Laevsky, I., Osenberg, O., Itskovitz-Eldor, J. 2008. Establishing a dynamic rocess for the formation, propagation, and differentiation of human embryoid bodies. Stem Cells Dev 17, 1227-1242.

Leor, J., Gerecht, S., Cohen, S., Miller, L., Holbova, R., Ziskind, A., Shachar, M., Feinberg, M. S., Guetta, E., Itskovitz-Eldor, J. 2007. Human embryonic stem cell transplantation to repair the infarcted myocardium. Heart 93, 1278-1284.

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