Research Group

  • Prof. Peter Lonai, Principal Investigator
  • Dr. Marat Gorivodsky, Research Associate

Location

  • Weizmann Institute of Science, Rehovot, Israel

Title

  • Can ES Cells Form a Specific Complex Organ?

Stem cell technology is one of the greatest advances of recent biology. Its first step was cloning of farm animals by transfer of embryonic cell nuclei into oocytes. Later, in the famous Dolly experiment, a sheep was cloned from somatic cell nuclei. This meant that transgenic animals can be made to produce pharmaceutical and other agents using nuclei from cells that express genes important for industry. These results also meant that the differentiated state of our cells is less stable than we thought. Knowing that stem cells, such as embryonic stem (ES) cells, can form multiple cell types, schemes were worked out to produce stem cell lines from somatic cells via nuclear transplantation into oocytes. Most recently, the great flexibility of adult stem cells was discovered. The possibility of cloning higher animals and even man, and the prospect of patient-derived cell therapy drew little attention. These results also revived interest in basic questions, such as the flexibility of the differentiated state, stem cell biology, and regeneration.

It is generally expected that stem cell technology will greatly advance biotechnology and cell therapy. Its application to organogenesis and to the production of organ grafts has however yet to be addressed. The importance of this problem, in the face of a chronic graft shortage, requires little emphasis.

The proposed research asks whether stem cells can contribute to the development of specific complex organs. We will use a loss-of-function mutation of Fgfr2 (fibroblast growth factor receptor 2) to analyse this question. This mutation completely abrogates limb development in mouse embryos. In preliminary experiments, ES cells injected into the prospective limb fields of the mutant caused outgrowth and chondrogenesis. We believe that a careful analysis of this experimental system, even if it may not yield complete limbs immediately, should bring us a few steps closer to making it feasible.