ABSTRACT
Cell therapy is a medical procedure that rebuilds structures and restores functions of deteriorated tissues or organs by stem cells. This approach is feasible in treatments of tissue dysfunction generated by trauma, infectious disease, degenerative processes caused by natural fatigue or environmental insults, or a natural consequence of senescence. The cellmediated regenerative medical interventions have a number of technical and biological limitations, which have stimulated new studies in biological processes and engineering. The advances in these two domains have created a multidisciplinary new field of biotechnology and bioengineering. The innovative work in this field has the potential for improving the quality of life of humans and significantly decreasing healthcare costs. The traditional use of cell therapy has been in bone marrow transplantation and treatment of autoimmune diseases. More recently, cell therapies have been applied with success in reparative surgery of soft tissues, skin and mucosa, peripheral nerve lesions, orthopedics including degenerative processes and trauma, angiogenesis, heart diseases, and stroke. The application of cell therapies is based on histological (homotopic
or heterotopic) and immunological (autologous transplants, allotransplants or xenotransplants) principles. Homotopic therapies are defined as procedures that use cells for repair and regeneration of the tissue from which they have been harvested. Good examples of homotopic therapies are: skin repair with in vitro expanded epidermal cells, isolation and implantation of pancreatic Langerhans islets (Eliaschewitz et al., 2004), and bone marrow aspiration to restore the hematopoietic tissue (Shizuru et al., 2005). Heterotopic therapies use stem cells obtained from a source different from that in which they are used. The most frequent source of stem cells used in repair of peripheral tissues is bone marrow. However, it is now known that many tissues, such as adipose or blood vessel walls, harbor pluripotent stem cells that can be used in repair and regeneration. This procedure depends upon the pluripotency of stem cells or their transdifferentiation, and the underlying molecular mechanisms are not well understood. The paracrine effect of implanted cells that may activate the resident cell progenitors
has to be taken into consideration, as well as modification of the intercellular environment following cell injection. Autologous transplants involve the transfer of cells, tissues, or organs
from the same individual. Conversely, allotransplants or allogeneic transplants use cells from different individuals within the same species. Xenotransplants involve transplantation or temporary use of organs or tissues from a different species (e.g. porcine to human). In cases of allotransplants and xenotransplants, the implanted cells are necessarily identified as foreign by the receptor’s immune system, which triggers an immune rejection process. In the case of bone marrow transplantation, the new immune system will be formed by transplanted cells of the donor. Therefore, the rejection will be donor versus receptor (graft versus host disease, GVHD). Allotransplants and xenotransplants are maintained by immunosuppressive therapies, which are aggressive and have to be maintained for long periods. Notwithstanding this drawback, allogeneic transplants are necessary to correct pathologies associated with modifications in the genome, mutations leading to cancer, or in which the patient’s cells are not able to promote repair and tissue regeneration. Heterotopic autologous therapies are at present the most frequently
explored in basic, preclinical, and clinical research. Since 1990, the multipotency of adult stem cells, mainly from the bone marrow, has allowed the possibility of repair and regeneration of different tissues using the cells of the patient. The best example of heterotopic autologous therapy is the use of stem cells from the bone marrow in the treatment of cardiac ischemia. The rationale for this application is the capacity of such stem cells to differentiate in situ into cell lineages of the receptor site. The main goal of this kind of therapy is to offer tissue repair as close as possible to the physiologically normal tissue without restrictions of histocompatibility, which is a problem in allotransplants and xenotransplants. It is hoped that in the future these therapies will be able to restore an entire organ, such as pancreas, heart, or kidney, without the immune rejection and the required immunosuppressive treatments.
