February 16, 2005
Pig Embryonic Cell Transplants May Work For Humans

An Israeli research team at the Weizmann Institute of Science in Rehovot, Israel has discovered that tissues can be transplanted from organs in developing pig embryos to produce functioning organs in mice if the tissues are extracted from pig embryo organs during an optimal time window that is specific to each organ. (same article here)

Scientists at the Weizmann Institute of Science have determined distinct gestational time windows for the growth of transplanted pig embryonic liver, pancreas and lung precursor tissue into functioning organs in mice. These findings -- appearing this week in PNAS online Early Edition -- could help enhance the chances for successful implementation of embryonic pig tissue in the treatment of a wide spectrum of human diseases.

The study, led by Prof. Yair Reisner of the Institute's Immunology Department, involved the extraction of embryos from sows at various stages of pregnancy and implantation of organ-committed cell tissue into immunodeficient mice. His novel approach did not involve the growth of any tissue in culture. The analysis of embryonic-tissue at various gestational ages revealed a unique pattern of growth and differentiation for each organ.

The potential of embryonic pig tissues as a new source for organ transplantation in humans has been advocated for more than two decades. Transplant too early, however, and the risk is undifferentiated embryonic tissue that can develop into undesirable and possibly malignant tissue, a type of tumor known as "teratoma." Transplant too late and the risk is that the tissues will have reached the stage where they have been marked with certain identifiers that trigger rejection by the new host.

The study demonstrated that maximal liver growth and function were achieved at the earliest teratoma-free gestational age (four weeks). The growth and functional potential of the pancreas occurred later (six weeks) and its optimal transplant age limit was defined by a decline in the insulin- secreting capacity beyond 10 weeks gestational age. Development of mature lung tissue containing essential respiratory system elements was observed at a relatively late gestational age. The sequence of transplanted organ development paralleled that of normal embryonic development in which the liver and pancreas precede the lungs.

"Disappointing results in past transplantation trials may be explained, at least in part, by these results," explains Reisner. Early studies that attempted to cure diabetic patients by implantation of pig embryonic pancreas, made use of late gestation tissue which is now shown to be inferior compared to the optimal six weeks gestational time.

In previous studies, Reisner's group demonstrated that transplanted human and pig kidney embryonic tissue could grow into miniature, functioning human or pig kidneys inside a mouse. His novel approach was a matter of timing: gestational age proved to be the key to successful kidney growth from transplanted embryonic tissue.

Some pretty simple knowledge (the optimal time to take the cells from each organ) may make possible trans-species organ cell transplants (a.k.a. xenotransplantation).

The key is to take cells from an organ during the period soon after it has started to form.

Growing new organs in humans from embryonic pig tissues may be feasible, researchers report, but the cells need to come from specific stages of an embryo's development. Using pig tissue to replace human organs could help patients with diseases such as diabetes, Parkinson's disease, and liver failure, but researchers have so far faced a challenge of balance. On the one hand, stem cells taken from very early in an embryo's development tend to develop tumors after transplantation, whereas tissue from adult organs face rejection by the recipient's immune system. Taking cells from an embryonic organ soon after it has begun to form may strike the ideal balance. To investigate the best time to harvest embryonic cells, Yair Reisner and colleagues took embryonic pig tissue that had begun to form particular organs at various developmental stages and transplanted them into mice. The researchers studied three types of organs--liver, pancreas, and lung--and found unique growth patterns. Optimal time windows were clearly seen for each organ. The authors say these findings may help in part to explain the failure of previous transplantation trials of pancreatic islets in diabetic patients.

This research was sponsored by a American-Israeli tissue transplantation biotech company called Tissera.

Other labs are working on making pigs genetically more compatible with humans by transferring human genes into pigs in order to grow up organs that are highly compatible with humans. See my previous posts "Human Genes Put Into Pig Sperm"and "Genetically Engineering Pigs for Xenotransplantation" for some details. The promise of the genetic engineering approaches is that potentially fully grown organs could be transferred from pigs to humans. Such transfers of fully formed organs might require immunosuppressive drugs to make them compatible. Whereas the transfer of starter cells from early embryo proto-organs may provide greater immunocompatibility.

The obvious advantage of transferring fully formed organs is that they can be used to save people's lives in cases of acute organ failure. When the liver or another vital organ has stopped working entirely there is not enough time to transfer some cells and wait for those cells to grow up into a complete organ. Full sized organs are needed to deal with emergencies. However, in cases where an organ is failing slowly the ability to gradually grow a replacement alongside of it offers the potential for a more immunocompatible replacement.

My guess is that in the future both the use of starter cells to grow replacement organs in a human body and the transfer of fully grown xenotransplants will become commonly used treatments for organ failures. These treatments might even be used in a complementary fashion. Get an emergency full sized xenotransplant organ with immunosuppressive drugs to meet an immediate emergency need and then once the patient is stabilized and healthy transfer in some more immunologically compatible cells to grow yet another organ that will serve as the permanent replacement.

In the longer run it seems reasonable to expect the development of techniques that allow the growth of full sized immunologically compatible organs. Alternatively, full sized organs will be grown up and then immune system modification therapies will be developed that will be able to adjust an immune system to teach it that a transplant organ should be treated as native tissue.

Share |      Randall Parker, 2005 February 16 02:56 PM  Biotech Organ Replacement


Comments
Mai Thanh Tung said at February 23, 2005 3:10 AM:

I'm a patient with heart failure. The Doctor said that he have to replace a valve of my heart. I'm very happy to know that "Get an emergency full sized xenotransplant organ with immunosuppressive drugs to meet an immediate emergency need and then once the patient is stabilized and healthy transfer in some more immunologically compatible cells to grow yet another organ that will serve as the permanent replacement.". I'm now ready for any experiment like this when scientists need.

Thanks for all of your affort.

Best Regards,

Tung

jayne rigney said at June 9, 2005 2:14 PM:

hello my name is jayne rigney we found out 6 months ago my dad had bowl cancer now it has spread to his liver ,i recently heard people with liver cancer can have a liver transplant with a pigs liver is this true?????/ and if it is ,is there a waiting list????.if it is true can u please send me some information on this please.if it is not true can u still let me know please i would be extremely grateful.

kind regards

jayne rigney

oppong said at March 17, 2006 12:11 PM:

i want to know whether this stem cell transplant can be used to reactivate the growth plate after it's closure or when it's about to close.

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