A R Migliaccio1. 1. Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Rome, Italy ; Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY, USA.
Abstract
BACKGROUND: Blood transfusion is current standard-of-care for genetic forms of anemia that would be otherwise lethal and allows implementation of aggressive cytotoxic/surgical therapies developed for numerous types of cancer. In developed countries the blood supply is adequate and sporadically even in excess. However, difficulties exist in finding blood with rare phenotypes to treat alloimmunized patients and the progressive ageing of the human population predicts that blood will become scarce by 2050. These considerations establish the need for the development of techniques to generate cultured red blood cell (cRBCs) as transfusion products. MATERIALS AND METHODS: Recent progress in cell culture techniques is revolutionizing organ replacement therapies. Two new disciplines, cell therapy and tissue engineering, have been developed to generate in vitro therapeutic products for a variety of applications ranging from skin grafts to organ-function repairs. It is currently believed that these advances will eventually allow ex-vivo production of various cell types in numbers so great that, in the case of red cells, would be clinically adequate for transfusion. RESULTS: Proof-of-principle in animal models indicate that cRBCs generated from murine embryonic stem cells protect mice from lethal anemia. Conditions to generate small amounts of clinical grade cRBCs have been established and the first-in-man administration of autologous cRBCs perfomed. The results of this trial indicate that cRBCs survive in vivo at least as long as their natural counterpart. DISCUSSION: These ground-breaking reports have raised great excitement for clinical evaluation of cRBCs for transfusion. However, skepticism still persist that production of cRBCs in numbers sufficient for transfusion will ever be possible. This paper will discuss diagnostic and clinical goals pursuable with numbers of cRBCs that may be generated with current technology. CONCLUSION: We are confident that development of relevant clinical goals achievable with current technologies will not only improve clinical care in transfusion medicine but will also foster studies to overcome scientific and technical barriers that render transfusion with cRBCs of the general population impractical today.
BACKGROUND: Blood transfusion is current standard-of-care for genetic forms of anemia that would be otherwise lethal and allows implementation of aggressive cytotoxic/surgical therapies developed for numerous types of cancer. In developed countries the blood supply is adequate and sporadically even in excess. However, difficulties exist in finding blood with rare phenotypes to treat alloimmunized patients and the progressive ageing of the human population predicts that blood will become scarce by 2050. These considerations establish the need for the development of techniques to generate cultured red blood cell (cRBCs) as transfusion products. MATERIALS AND METHODS: Recent progress in cell culture techniques is revolutionizing organ replacement therapies. Two new disciplines, cell therapy and tissue engineering, have been developed to generate in vitro therapeutic products for a variety of applications ranging from skin grafts to organ-function repairs. It is currently believed that these advances will eventually allow ex-vivo production of various cell types in numbers so great that, in the case of red cells, would be clinically adequate for transfusion. RESULTS: Proof-of-principle in animal models indicate that cRBCs generated from murine embryonic stem cells protect mice from lethal anemia. Conditions to generate small amounts of clinical grade cRBCs have been established and the first-in-man administration of autologous cRBCs perfomed. The results of this trial indicate that cRBCs survive in vivo at least as long as their natural counterpart. DISCUSSION: These ground-breaking reports have raised great excitement for clinical evaluation of cRBCs for transfusion. However, skepticism still persist that production of cRBCs in numbers sufficient for transfusion will ever be possible. This paper will discuss diagnostic and clinical goals pursuable with numbers of cRBCs that may be generated with current technology. CONCLUSION: We are confident that development of relevant clinical goals achievable with current technologies will not only improve clinical care in transfusion medicine but will also foster studies to overcome scientific and technical barriers that render transfusion with cRBCs of the general population impractical today.
Authors: Greggory J Housler; Toshio Miki; Eva Schmelzer; Christopher Pekor; Xiaokui Zhang; Lin Kang; Vanessa Voskinarian-Berse; Stewart Abbot; Katrin Zeilinger; Jörg C Gerlach Journal: Tissue Eng Part C Methods Date: 2011-12-28 Impact factor: 3.056
Authors: Shi-Jiang Lu; Qiang Feng; Jennifer S Park; Loyda Vida; Bao-Shiang Lee; Michael Strausbauch; Peter J Wettstein; George R Honig; Robert Lanza Journal: Blood Date: 2008-08-19 Impact factor: 22.113