Transplantation has come a long way from the first, not always successful experiments to nowadays, when doctors save thousands of lives. Transplantation has become an effective treatment for severe diseases of vital organs, and for many diseases (kidney disease, heart or liver) organ transplantation has become clinically routine. But on the other hand, limited “availability” of donor organs, transplant rejection, immune reactions, side effects caused by immunosuppressive therapy – all these factors limit the transplantation medicine. That is scientists all over the world consider and develop alternative methods of transplantation, that in future could replace organs transplantation and could help in saving human lives.
In modern transplantation in most cases are used organs and human tissue, but the priorities are to develop methods of preserving organs and tissues, improvement of schemes of immunosuppressive therapy, cell transplantation, xenotransplantation and artificial organs. An alternative to using organs or tissues may be the use of stem cells. In recent years increases worldwide attention to stem cell research in terms of their clinical use, as experts say stem cells can be successfully used in autologous cell and tissue therapy that has several advantages over transplanting whole organs.
In the paper it is necessary to consider what are the stem cells and what are the prospects for their use in cell therapy and transplantation.
Organ replacement and transplantation
Organ transplantation has been one of the most prominent and promising advances in the science in the 20th century, as prolongation of life by replacing damaged organs, which previously seemed like a dream, became a reality. Transplantation has become an effective treatment for severe diseases of human organs, and in most cases for replacement are used human organs and tissue. (Cerilli 1988)
Transplant is an operation to replace a viable organ, tissue and cells from one individual to another. Organ or tissue used for transplant is called a graft. Donor is called a man who gives his tissues or organs for transplant to someone else. Recipient is a man who is transplanted an organ, tissue or cells of another organism for therapeutic purposes. Donors can be living family members and living donors with no genetic relationship (husband, wife, friends, close friends). (Forsythe 2000)
It is possible to distinguish allotransplantation, which is transplanting organs and tissues from one person to another on the principle of compatibility. Autotransplantation involves transplantation within a single organism. Xenotransplantation is transplantation of organs, tissues and cells of animals to humans. Also there are several types of transplantation, depending on the location of the transplanted organ or tissue. When an organ is transplanted to its anatomical location, we should speak of orthotopic transplantation, and when organ is transplanted to another place, it is called heterotopic transplantation. (Forsythe 2000)
Fundamental issue in determining the success of the operation and fate of the transplanted organ is the selection of compatible donor-recipient pairs. It is essential that the blood group of donor and recipient should match, otherwise the graft does not take hold. Rejection of a transplanted organ is the most frequent complication in the postoperative period, and also it is the most frequent and serious of all known transplant complications. The reason for its development is antigenic differences between donor and recipient, that is why the possibility of developing this complication is significantly lower in organ transplantation from a living related donor. (Forsythe 2000)
The operation of replacement takes about 6-8 hours, and the time during which the organ transplant can be outside of the body should be as small as possible. Before operation on transplant organs from one person to another must be solved two different set of problems. The first problem is the reunification of the circulatory system of the recipient with the transplanted organ, in order it could receive and maintain blood supplied with oxygen and nutrients. This requirement is now fully satisfied by the advanced surgical methods (for example, a technique of microsurgery), the development of miniaturized surgical instruments and extremely sharp, thin needles that are connected to the subtle but strong suture material. Using a microscope modern surgeons now are able to sew tiny arteries and veins, providing them with leakproof connection to a suitable vessel of donor organ. The second type of problems are connected with the immunological rejection of donor organs. Despite the high level of achievements of modern medicine, the problem of rejection was not resolved by the end. When the alien tissue is put in the body, it is immediately inspected by the immune system cells, and its surface markers (antigens) are checked against antigens of the body cells, and if they do not fit, the immune system will immediately begin a massive attack on the foreign tissues. Millions of white blood cells congregate around the alien tissue, attacking it with poisonous substances, and as a result the graft inflames and sores, and after a while it dies. This happened with all transplants (excluding cases of transplant between identical twins, and transplant of the cornea), which were placed before the detailed study of the immune system. With adequate immunogenetic selection there is possibility that the transplanted organ would adapt to the body of the recipient. (Cerilli 1988)
One of the important phases of the operation, which largely ensures its success and ensuring the restoration of organ function, is the preservation of donor organ. The criterion for successful conservation should be the maximum efficiency of preserving the viability and functional use of donor material for extremely long time.
The next important problem of transplantation is growing number of people who need transplants. In this regard, researchers are beginning to seriously engaged in development of possibilities of the use of animal organs and tissues for transplantation to man for therapeutic purposes – xenotransplantation. It should be noted that currently the global scientific community is wary of this type of transplantation, and the cause is not only in the unresolved problem of the physiological compatibility of humans and animals, but mainly in the risk of disease transmission from animals to humans. That is why scientists around the world are working on creation of artificial organs, which could replace natural organs by their functions.
One more important issue in recent years is active research in the direction of stem cell transplantation, which are precursors of various types of cells, and are the first unique “building material” from which later are formed organs and tissues. The first successful attempts to stem cell transplantation in cardiology, orthopedics and traumatology confirm the great positive perspectives of this new direction. (Pollak et al., 2002)
Embryonic stem cells transplantation
Recent years are characterized by a revolution in the study and use of stem cells. The concept of “stem cells” has long history, but previously it was used mainly in relation to hematopoietic cells. According to the modern definition, stem cells are undifferentiated cells which have the ability to division for a long time, often throughout the life of the organism. Under certain conditions – if the signals of differentiation – such cells can turn into different cell types, that is, have the potential to develop into mature cells with specific size and shape and have specialized functions (such as heart muscle cells, nerve cells, chondrocytes, and so etc.) (Gerlach 2002)
Stem cells can be classified according to their origin: for example, embryonic stem cells are called cells derived from the inner cell mass blastocyst (one of the earliest stages of embryo development), which are pluripotent, that means are capable of developing into all types of body cells. For the first time human embryonic stem cells were obtained in 1998 (Thomson 1998)
From the viewpoint of applications in regenerative medicine these cells are ideal. So, when placed into the affected animal organs or differentiated cells (cardiomyocytes, neuronal cells), got from embryonic stem cells, it is observed their integration into the defective tissue and expression of tissue-specific functions. That shows and proves great potential of the use of stem cells in transplantation.(Wobus 2001)
However, due to ethical problems in most countries in the world research associated with obtaining human embryonic stem cells is prohibited, and now such works do not find clinical application. Continued research with embryonic stem cells is possible using stable cell lines, obtained in vitro, but such cells can be used in cell and tissue therapy only after obtaining positive results on several issues. This applies to methods of directed differentiation of embryonic stem cells and the selective isolation of pure populations of specific cell types, evidence of the absence of tumor activity derived somatic cells, as well as immunologic incompatibility between donor cells and the host organism. Another alternative possibility of obtaining donor cells for tissue transplantation is the use of somatic adult stem cells, and in the last 4-5 years of research in this direction are carried out very intensively. Adult stem cells are undifferentiated (unspecialized) cells that are found in a differentiated (specialized) tissue. Adult stem cells were found in many tissues of the human body that have a powerful regenerative capacity (for example, bone marrow, haematopoietic and mesenchymal cells that already have a clinical application in cell therapy in patients with leukemia and in bone regenerative therapy, respectively, and the mesenchyme, neurons, placenta, blood vessels, adipose tissue, pancreas, liver, muscle, skin), as well as in tissues with low regenerative capacity (for example, adult brain), and these cells can be activated.
Unlike embryonic stem cells, the use of adult stem cells is not connected with ethical problems. In addition, in the case of stem cell there is no immunological conflict. The concept of therapy with autologous stem cells lies in the selection of adult stem cells, the use of technology in vitro for multiplication and differentiation of cells in diseased tissue, and then for their use for transplantation. (Gerlach 2002)
Examples of specific clinical applications are: restoration of the damaged heart muscle by injection of cells in the diseased region of the heart, the introduction of progenitor cells from a healthy liver in liver cirrhosis affected; injection of neural stem cells into cells of the central nervous system.
But to date there are a lot of open issues and specific problems on the medical use of embryonic and adult stem cells. However, due to the great prospects of the therapeutic use of these cell types it is necessary to conduct a large number of studies comparing their potential. The advantages of using autologous adult stem cells for transplantation medicine are obvious: unlimited access, short waiting times result (in contrast to the situation with artificial organs) and the absence of immunosuppressive therapy with its negative side effects. At the same time, the stem somatic cells got from adult organism may contain DNA abnormalities caused by environmental factors, as well as age-related defects. (Gerlach 2002)
Scientists hope to create in the near future on the basis of Stem cells full tissues and organs, needed for transplant to patients instead of donor organs, and their advantage would be complete immunologic compatibility. Thus, the cell and tissue therapy, which nowadays is developing very rapidly, is an important and promising area of medicine, but it requires a lot of clinical research to accelerate its wide application in practice.
Cerilli G. James. Organ transplantation and replacement. Lippincott, 1988
Forsythe John L. R. Transplantation: a companion to specialist surgical practice. Elsevier Health Sciences, 2005
Gerlach J. C., Zeilinger K. “Adult stem cell technology – prospects for cell based therapy in regenerative medicine”. The Int. J. of Artificial Organs, Vol. 25, № 2, 2002. P. 83–90.
Mezey E. K. J., Chandross et al. “Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow”. Science Vol. 29, № 5497, 2000. P. 1779–1782.
Pittenger M. F., Mackay A. M., Beck S. C. et al. “Multilineage potential of adult human mesenchymal stem cells”. Science Vol. 284, 1999. P. 143–147.
Pollak Julia M., Hench larry l. Future strategies for tissue and organ replacement. 2002
Sell S. Stem cells handbook. Humana Press 2000
Thomson J. A., Itskovitz-Eldor J., Shapiro S. S. et al. “Embryonic stem cell lines derived from human blastocysts”. Science, Vol. 282, 1998. P. 1145–1147.
Wobus A. M. “Potential of embryonic stem cells”. Molecular Aspects of Medicine, Vol. 22, 2001. P. 149–164.