December 22, 2002
Israeli Team Grows Mini Human Kidneys In Mice

Prof. Yair Reisner of the Weizmann Institute of Science in Rehovot Israel is the leader of a team that has successfully grown functional kidneys in mice from pig and human stem cells taken from embryos.

Reisner and Ph.D. student Benny Dekel of the Weizmann Institute's Immunology Department, with Prof. Justen Passwell, the head of the pediatric department at the Sheba Medical Center, transplanted human and porcine "kidney precursor cells" (stem cells that are destined to become kidney cells) into mice. Both human and porcine tissues grew into perfect kidneys, the size of the mice's kidneys. The miniature human and pig kidneys were functional, producing urine. In addition, blood supply within the kidney was provided by host blood vessels as opposed to donor blood vessels, greatly lowering the risk of rejection.

The scientists pinpointed the ideal time during embryonic development in which the stem cells have the best chance to form well-functioning kidneys with minimal risk for immune rejection. Their findings suggest that 7-8 week (human) and 4 week (porcine) tissue offers an optimal window of opportunity for transplantation. If taken at earlier time points the tissues will develop disorganized tissue that would include non-kidney structures such as bone, cartilage, and muscle. If taken at later time points the risk for immune rejection is substantial.

Within this optimal time range the tissue doesn't contain certain cells that the body recognizes as foreign (antigen-presenting cells), the scientists found. These cells, which originate in the blood system, reach a developing kidney only after ten weeks.

After growing the human and porcine kidney tissue in mice, the scientists checked how human lymphocytes (fighter cells in the immune system) might react to it. They injected human lymphocytes into immunodeficient mice (that have no immune system and thus do not interfere with the immune response). The findings were encouraging: as long as the kidney precursors were transplanted within the right time range, the lymphocytes did not attack the new pig or human kidneys – despite the fact that lymphocytes and kidney precursors originated from different donors. Immune rejection was also tested in normal mice and was shown to be reduced compared to that induced by precursors from later time points.

There is an obvious problem for the use of this approach in the United States: The precursor stem cell tissue has to be harvested from 7-8 week old human embryos (which were aborted embryos). The idea of allowing an embryo to develop for 2 whole months before harvesting will elicit strong opposition from the opponents of embryonic stem cell use. An attempt to make organs available which are grown by this method (whether from abortions or from embryos grown in a lab) may well lead the US Congress to outlaw the technique.

As an alternative approach there is a chance that pig embryonic stem cells could be coaxed into forming kidneys that would be immunologically compatible with humans and compatible with human metabolic needs for kidney function. That is likely the reason why the Israeli group also used porcine stem cells in this set of experiments. But the use of porcine stem cells to create human-compatible kidneys may be technically harder than the use of human stem cells for the same purpose. In order to make the porcine stem cell approach work it may be necessary to put human versions of some genes into pigs.

Another alternative approach would be to figure out how to instruct cells that are more differentiated to become less differentiated cell types. Then it might be possible to, for instance, tell an adult kidney cell to revert back to the state that its progenitors were in at the 7th or 8th week of embryonic development. It is difficult to say how long it would take to develop a way to do that. By contrast, the ethically and legally more problematic approach of allowing a human embryo to develop thru the series of steps it normally goes thru is technically well understood and doesn't require as much knowledge of how cells differentiate. Therefore what is today the easiest technical approach also happens to be the approach that elicits the greatest political opposition.

Update: Charles Murtaugh corrects my sloppy use of the term "embryonic stem cells" (which you will no longer see above since I fixed it). In these experiments the embryos were sufficiently far along in their development that the cells taken from the embryos had undergone enough differentiation that they were no longer capable of becoming all cell types (i.e. no longer pluripotent). Therefore they were not embryonic stem cells (which are pluripotent and undifferentiated) even though they were stem cells extracted from embryos. So what to call these cells? The widely used term "adult stem cells" hardly seems adequate to describe stem cells that are not pluripotent but which come from an embryo. The word "adult" implies cells rather older than those used in this experiment and stem cells taken from an adult wouldn't have the same qualities. Though some writers use the term "non-embryonic stem cells" it seems to my ear that "non-pluripotent stem cells" would be an even more precise term.

By Randall Parker at 2002 December 22 09:32 PM  Biotech Organ Replacement

Comments
Nofit Milstein said at December 25, 2002 2:15 AM:

The research performed at the Weizmann Institute made use of aborted embryos - no embryos were harvested for this research. You can see AP's clarification at:
http://abcnews.go.com/wire/Living/ap20021224_1165.html

Randall Parker said at December 25, 2002 10:24 AM:

Nofit, thanks for pointing this out. Though I doubt that will make it any less morally objectionable to the people who would object to it. There's a pretty big overlap between those who morally object to abortion and those who morally object to the use of embryonic stem cells.

Eyal Arazi said at June 14, 2003 8:02 AM:

Where exactly were the cells transplanted in the mouse's body? what does it mean "These cells, which originate in the blood system, reach a developing kidney only after ten weeks"

Im a student who studies in the technion- israel, Master degree in bio-medicine department and im really interested in your work.

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