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Latest culture techniques: cracking the secrets of bone marrow to mass-produce erythrocytes and platelets ex vivo
Ferrata Storti Foundation
Haematologica 2021 Volume 106(4):947-957
Christian A. Di Buduo,1 Alicia Aguilar,1 Paolo M. Soprano,1 Alberto Bocconi,1,2 Carolina P. Miguel,1 Giovanna Mantica1 and Alessandra Balduini1,3
1Department of Molecular Medicine, University of Pavia, Pavia, Italy; 2Department of Chemistry, Materials and Chemical Engineering G. Natta, Politecnico di Milano, Milano, Italy and 3Department of Biomedical Engineering, Tufts University, Medford, MA, USA
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 chal- lenging 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 instru- mental 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 tar- geted therapies for thrombocytopenia and anemia, but also a long-term promise for new approaches to the understanding and cure of hemato- logic diseases.
Introduction
The importance of three-dimensional (3D) tissue systems has grown substantive- ly in recent years as laboratory tools that recapitulate the physiological architecture of native human tissues.1 The bone marrow represents a challenging organ to reproduce because of its structure and complexity within the bone cavity.2 Recent research in the field aims to overcome the problems by developing different 3D models for the ex vivo production of blood cells. These systems can be used to understand the process of hematopoiesis in normal conditions and disease states and as an innovative way to produce blood products for clinical needs.
More than 100 million units of blood are reported to be collected worldwide every year. Nevertheless, in no country does the contribution of volunteers succeed in coping with the growing demand, making it necessary to create alternative methods for the production of blood cells.3 There is particular interest in the possi- bility of producing erythrocytes and platelets.
Platelets are needed more than other blood components because they are perish- able. While erythrocytes can be refrigerated and used for up to 6 weeks and plasma can be frozen for as long as a year, platelets must be kept at room temperature to maintain their shape and function, which means that they have a shelf-life of only 5 days inside transfusion bags.4 Overall, blood products for transfusion are often unavailable in low-income and middle-income countries.5,6 Furthermore, even in developed countries, outside of large and medium-sized cities, hospitals can run out of platelets and erythrocytes when donation rates are down, which occurs mainly during the summer or public health emergencies, such as a pandemic. In the last few years, emerging infectious diseases have captured the attention of the transfusion medicine community and measures have been implemented to address
Correspondence:
CHRISTIAN A. DI BUDUO
christian.dibuduo@unipv.it
ALESSANDRA BALDUINI
alessandra.balduini@unipv.it
Received: September 25, 2020. Accepted: December 11, 2020. Pre-published: January 21, 2021.
https://doi.org/10.3324/haematol.2020.262485
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