There is no doubt that the blood transfusion saves lives. Haemorrhages, malignant diseases of the blood, coagulation disorders do not necessarily constitute a threat to human life when the transfusion of blood or its components can be used. Unfortunately, despite numerous actions promoting honorary blood donation, there is a huge disproportion between the number of donors and the actual demand for blood in hospitals. The needs are massive – in Poland alone 2 000 000 transfusions are performed a year.
Blood transfusion is associated with the risk of various complications, among which is the most severe are: septic shock, anaphylactic shock, acute hemolytic reaction, transfusion-related acute respiratory failure and late complications such as contraction of diseases (syphilis, AIDS, malaria, hepatitis), delayed hemolytic transfusion reaction, or transplant against host reaction. Scientists have been looking for the solution to obtain blood without having to grapple with the risk of serious side effects. Artificial blood has a huge advantage over the blood collected from donors, including lower risk of pathogens transmission, serological incompatibility, and furthermore offers extended survival of the RBC. Red blood cells (RBCs) are produced ex vivo from various precursor cell (somatic “adult” stem cells, human embryonic stem cells or induced pluripotent stem cells) and with the use of synthetic biomaterials.
In the production of red blood cells from somatic stem cells there is a low risk of malignant degeneration and infections, but the ability of self renewal, essential for mass production of blood cells, in this case is limited. The problem of tissue incompatibility is comparable with that noted in blood drawn from donors. Unfortunately it is almost impossible to produce blood cells in a large scale with the use of this method, which excludes it from the general use in the future.
Both embryonic stem cells and induced pluripotent stem cells (iPS) provide material for an infinite number of cells, at the same time giving the possibility to obtain RBC phenotypes identical to blood drawn from the universal donor. Unfortunately, the current method of obtaining embryonic or induced pluripotent stem cells is still associated with a lot of controversies on the moral background. It also brings difficulty in assessing the risk of transmission of pathogens and malignanant transformation (especially in the case of induced pluripotent cells, while using oncogene containing vectors). The generation of mature erythrocytes out of embryonic stem cell today is carried out according to different models depending on the research centre. One of the methods involves the production of red blood cells from hemangioblasts (yielding 30-65% of the fully developed mature RBCs) with the use of a wide range of cytokines (such as BMP4, VEGF165, or thrombopoietin). RBCs obtained obtained in this way initially exhibit expression of fetal and embryonic hemoglobin, but during the subsequent in vitro culture they maturate into adult hemoglobin HbA. In another method, the cells are derived from hematopoietic stem cells by co-culture with murine fetal liver-derived stromal cells. Globin expression in the cell cultures derived from embryonic stem cells change over time from embryonic to adult type. They also are characterized by a satisfactory level of dehydrogenase glucose-6-phosphate activity.
Promising results obtained under the guidance Sifinejad have managed to induce pluripotent stem cells from dermal fibroblasts with Bombay phenotype (antigen free), through the ectopic expression of transcription factors Klf4, Oct4, Sox2 and c-Myc. Bombay type characterized by a lack of ABH-antigens as a result of the absence of H gene (FUT1) and secretor gene (FUT2). Undoubtedly, this is another step towards the production of universal blood suitable for recipients of all ABH blood types.
Recent discoveries in biotechnology, nanotechnology, molecular biology and polymer chemistry, contributed to the creation of biomaterials such as liposomes or polymeric nanoparticles. Is there any chance that artificial red blood cells will be mass-produced in laboratories? This would mean getting rid of the problem of infections, adverse immune reactions as well as enabling longer storage thanks to increased stability of the artificial blood cells. Researchers led by Doshi decided to use biomimetic strategy, through the synthesis of molecules similar to red blood cells, but made out of biocompatible, biodegradable PLG (polylactic-co-glycolide), incubated in 2-propanol. Hemoglobin was absorbed on the surface and cross-linked with glutaraldehyde with the subsequent dissolution of the core. In order to increase the capacity to transfer oxygen molecules the structure has been strengthened with an additional chain of hemoglobin. The generated artificial red blood cells are characterized by nearly identical morphology, ability to carry oxygen, size, flexibility and stretch ratio like natural red blood cells.
Although this is a promising opening to the new chapter in the transfusion medicine, scientists have to face the biggest enemy of progress – the cost of production, as well as perform many successive tests which will show the true clinical efficacy of new treatment solutions for transfusions before they are approved for a routine use. Developing an effective and safe substitute for blood obviously needs further determination and time.
1.Red blood cell transfusion strategies Transfusion Clinique et Biologique Volume: 8, Issue: 3, June, 2001, pp. 207-210 Blajchman, M.A.; Hébert, P.C.
2.Ex-vivo red blood cells generation: A step ahead in transfusion medicine? European Journal of Internal Medicine Volume: 22, Issue: 1, February, 2011, pp. 16-19 Lippi, Giuseppe; Montagnana, Martina; Franchini, Massimo
Sickle cell anemia is one of the indications for blood transfusion. Want to know more? Watch on medtube.net: “Sickle cell anemia”