Latest culture techniques: cracking the secrets of bone marrow to mass-produce erythrocytes and platelets <i>ex vivo

Abstract

Since the dawn of medicine, scientists have carefully observed, modeled and interpreted the human body to improve healthcare. At the beginning there were drawings and paintings, now there is three-dimensional modeling. Moving from two-dimensional cultures and towards complex and relevant biomaterials, tissue-engineering approaches have been developed in order to create three-dimensional functional mimics of native organs. The bone marrow represents a challenging organ to reproduce because of its structure and composition that confer it unique biochemical and mechanical features to control hematopoiesis. Reproducing the human bone marrow niche is instrumental to answer the growing demand for human erythrocytes and platelets for fundamental studies and clinical applications in transfusion medicine. In this review, we discuss the latest culture techniques and technological approaches to obtain functional platelets and erythrocytes ex vivo. This is a rapidly evolving field that will define the future of targeted therapies for thrombocytopenia and anemia, but also a long-term promise for new approaches to the understanding and cure of hematologic diseases.

Sirtuin 6 Regulates the Activation of the ATP/Purinergic Axis in Endothelial Cells

“…When megakaryocyte progenitors were cocultured with SIRT6+ HUVECs, we observed comparable terminal differentiation with respect to cells cocultured with pBP, as demonstrated by the analysis of the late-differentiation markers, integrin β3 (CD61) and glycoprotein Ib (CD42b) ( Figure 2 A,B). Physiologically, megakaryocytes undergo successive rounds of endomitosis during differentiation, resulting in polyploidy [ 19 ]. Here, we demonstrated that both conditions support efficacious polyploidization with no significant differences between the two tested conditions ( Figure 2 C).…”

Highly efficient platelet generation in lung vasculature reproduced by microfluidics

“…Finally, the work introduces a novel system for generating platelets in vitro, by multiple passage of MKs through a micro uidic chamber. Current systems developed to generate platelets in vitro include 2D and 3D culture systems, 3D bioreactors and big tank bioreactors, the latter using turbulence to generate platelets from MKs [47][48][49] . Thon et al developed a micro uidic system that applies shear to emergent proplatelets from MKs 50 .…”

Illustrated State‐of‐the‐Art Capsules of the ISTH 2022 Congress

“…Leading studies point to the bone marrow niche as the core of hematopoietic stem cell (HSC) differentiation, revealing interesting and complex environmental factors for consideration. Megakaryocytes take cues from the physicochemical bone marrow microenvironment, which includes contact with extracellular matrix components, interaction with endothelium, and contact with the turbulent flow generated by the blood circulation into the sinusoid lumen 10 . Germinal and acquired mutation in HSCs may manifest in altered megakaryocyte maturation, proliferation, and platelet production.…”

“…Megakaryocytes take cues from the physicochemical bone marrow microenvironment, which includes contact with extracellular matrix components, interaction with endothelium, and contact with the turbulent flow generated by the blood circulation into the sinusoid lumen. 10 Germinal and acquired mutation in HSCs may manifest in altered megakaryocyte maturation, proliferation, and platelet production. Alterations of the whole hematopoietic niche may also occur, highlighting the central role of megakaryocytes in the control of the physiological bone marrow homeostasis.…”