Page 34 - 2021_04-Haematologica-web

C.A. Di Buduo et al.
ity, enzyme content, capacity of their hemoglobin to fix/release oxygen, and expression of blood group anti- gens.52 Nevertheless, these cell sources usually derive from clinical procedures and can be rare and difficult to obtain. They require a continuous supply of donors due to the limited expansion potential, making it difficult to hypoth- esize their usage for clinical applications. In this regard, Trakarnsanga et al. developed an alternative approach, immortalizing early bone marrow adult erythroblasts and generating a stable line functionally identical to adult donor erythrocytes.53 This cell line revealed promising properties for manufacturing red blood cell products and as a research tool for the study of erythropoiesis in health and disease. Compared to umbilical cord blood-derived immortalized human erythroid progenitor cell lines, this source demonstrated better performance and recapitula- tion of adult erythropoiesis.54
The need for cells that could overcome the limits related to donor dependence have prompted researchers to use human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC). hESC have been grown either on stromal cells or in feeder-free and serum-free cul- tures to produce platelet-like particles displaying function- al and morphological features comparable to peripheral blood platelets, but with limited long-term self-replication of megakaryocyte progenitors and consequent yield of platelets.55 hESC have also been proposed as a source of stem cells to generate universal red blood cells,56 but with some limitations in terms of cell survival and end-stage maturation.
Good outcomes have been obtained with hiPSC, which overcome ethical concerns related to the use of cells of embryonic origin. The physiological features of hiPSC- derived megakaryocytes resemble those of peripheral
Figure 2. Overview of sources of stem cells for producing platelets and erythrocytes in vitro. Different stem cell sources have been studied for their potential to gen- erate platelets and erythrocytes in vitro. Primary cells can be obtained either from human or mouse bone marrow, or derived from human peripheral blood and umbil- ical cord blood hematopoietic stem cells. Furthermore, immortalized cell lines have been generated from human embryonic stem cells, human-induced pluripotent stem cells and adipose-derived mesenchymal stromal/stem cell lines. HSC: hematopoietic stem cells; hESC: human embryonic stem cells; hiPSC: human-induced pluripotent stem cells, ASC: adipose-derived mesenchymal stromal/stem cells. The figure was created using Servier Medical Art templates licensed under a Creative Commons Attribution 3.0 Unported License (https://smart.servier.com).
950
haematologica | 2021; 106(4)