An Overview of Different Strategies to Recreate the Physiological Environment in Experimental Erythropoiesis

Abstract

Human erythropoiesis is a complex process leading to the production of mature, enucleated erythrocytes (RBCs). It occurs mainly at bone marrow (BM), where hematopoietic stem cells (HSCs) are engaged in the early erythroid differentiation to commit into erythroid progenitor cells (burst-forming unit erythroid (BFU-E) and colony-forming unit erythroid (CFU-E)). Then, during the terminal differentiation, several erythropoietin-induced signaling pathways trigger the differentiation of CFU-E on successive stages from pro-erythroblast to reticulocytes. The latter are released into the circulation, finalizing their maturation into functional RBCs. This process is finely regulated by the physiological environment including the erythroblast-macrophage interaction in the erythroblastic island (EBI). Several human diseases have been associated with ineffective erythropoiesis, either by a defective or an excessive production of RBCs, as well as an increase or a hemoglobinization defect. Fully understanding the production of mature red blood cells is crucial for the comprehension of erythroid pathologies as well as to the field of transfusion. Many experimental approaches have been carried out to achieve a complete differentiation in vitro to produce functional biconcave mature RBCs. However, the various protocols usually fail to achieve enough quantities of completely mature RBCs. In this review, we focus on the evolution of erythropoiesis studies over the years, taking special interest in efforts that were made to include the microenvironment and erythroblastic islands paradigm. These more physiological approaches will contribute to a deeper comprehension of erythropoiesis, improve the treatment of dyserythropoietic disorders, and break through the barriers in massive RBCs production for transfusion.

Comprehensive phenotyping of erythropoiesis in human bone marrow: Evaluation of normal and ineffective erythropoiesis

“…As the availability of human bone marrow samples is limited, in vitro culture of CD34 + HSPCs has been widely used as a model of human normal and disordered erythropoiesis. [31][32][33][34][35][36] However, differences between in vitro models and "true" in vivo erythropoiesis in human bone marrow exist. While the functional features of erythroid progenitors and erythroblasts are largely similar between these two systems, some differences exist.…”

Blood Pharming – eine realistische Option?

“…Die Interaktion zwischen Makrophagen und Erythroblasten wird zum einen durch direkte Zell-Zell-Kontakte und zum anderen durch verschiedene lösliche Faktoren gewährleistet. Eine Reihe von Zelladhäsionsmolekülen (CXCL12/CXCR4, P-Selektin/ PSGL-1 sowie VCAM-1/VLA-4-Selektin) und ihre Wechselwirkung in den EBIs sind für die Inselintegrität von entscheidender Bedeutung [28]. Zudem sind eine Reihe spezieller Zytokine an der Reifung erythroider Zellen beteiligt.…”

Mercury Chloride Impacts on the Development of Erythrocytes and Megakaryocytes in Mice

“…In the process of erythro-megakaryopoiesis, erythroid-megakaryocyte progenitors (EMPs) are capable of differentiating into both erythrocytes and megakaryocytes/platelets, with several intermediate steps including erythroid progenitors (EPs) and megakaryocyte progenitors (MkPs) [ 9 ]. EPs are comprised of two stages of progenitors, including the earlier burst-forming units-erythroid progenitors (BFU-Es) and the later colony-forming units-erythroid progenitors (CFU-Es) [ 10 ]. CFU-Es further differentiate into erythroblasts, which eventually lose their nuclei and become mature erythrocytes [ 10 ].…”

“…EPs are comprised of two stages of progenitors, including the earlier burst-forming units-erythroid progenitors (BFU-Es) and the later colony-forming units-erythroid progenitors (CFU-Es) [ 10 ]. CFU-Es further differentiate into erythroblasts, which eventually lose their nuclei and become mature erythrocytes [ 10 ]. On the other hand, MkPs give rise to megakaryocytes and ultimately yield platelets [ 11 ].…”