Ex vivo generation of transfusable red blood cells from various stem cell sources: A concise revisit of where we are now.

Blood transfusion is an essential and irreplaceable part of modern medicine, as a therapeutic modality or additional support to other clinical therapies. Nevertheless, the entire procedure from blood collection to administration, absorbs a significant amount of resources and has a number of problems that need to be addressed. The paucity of donors, the transmission of pathogenic microorganisms and the overall costs of the process have switched the scientific interest to the quest of alternative transfusion methods. The industrial ex vivo production of transfusable red blood cells capable of replacing a unit of packed red blood cells is a very attractive prospect, let alone the idea of a massive production of such a biological material. Various scientific groups, by exploiting erythropoiesis, the stem cells' characteristics and the constantly renewed knowledge in the fields of collection, culture, preservation and expansion of stem cells, have made significant progress towards the realization of such an idea. All three major sources of stem cells, haematopoietic stem/progenitor cells, human embryonic stem cells and induced pluripotent stem cells are thought to be capable of generating adequate amounts of red blood cells. By further studying and refining the in vitro red cell production protocols, it is anticipated that the economic and biotechnological obstacles of the current methods will be overcome in the near future. This manuscript is a brief revisit of their current state of the art, potentials and obstacles that are associated with industrial and clinical application issues.