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Concise review: stem cell-derived erythrocytes as upcoming players in blood transfusion.

ABSTRACT: Blood transfusions have become indispensable to treat the anemia associated with a variety of medical conditions ranging from genetic disorders and cancer to extensive surgical procedures. In developed countries, the blood supply is generally adequate. However, the projected decline in blood donor availability due to population ageing and the difficulty in finding rare blood types for alloimmunized patients indicate a need for alternative red blood cell (RBC) transfusion products. Increasing knowledge of processes that govern erythropoiesis has been translated into efficient procedures to produce RBC ex vivo using primary hematopoietic stem cells, embryonic stem cells, or induced pluripotent stem cells. Although in vitro-generated RBCs have recently entered clinical evaluation, several issues related to ex vivo RBC production are still under intense scrutiny: among those are the identification of stem cell sources more suitable for ex vivo RBC generation, the translation of RBC culture methods into clinical grade production processes, and the development of protocols to achieve maximal RBC quality, quantity, and maturation. Data on size, hemoglobin, and blood group antigen expression and phosphoproteomic profiling obtained on erythroid cells expanded ex vivo from a limited number of donors are presented as examples of the type of measurements that should be performed as part of the quality control to assess the suitability of these cells for transfusion. New technologies for ex vivo erythroid cell generation will hopefully provide alternative transfusion products to meet present and future clinical requirements.

SUBMITTER: Zeuner A

PROVIDER: S-EPMC3697769 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Concise review: stem cell-derived erythrocytes as upcoming players in blood transfusion.

Zeuner Ann A Martelli Fabrizio F Vaglio Stefania S Federici Giulia G Whitsett Carolyn C Migliaccio Anna Rita AR

Stem cells (Dayton, Ohio) 20120801 8

Blood transfusions have become indispensable to treat the anemia associated with a variety of medical conditions ranging from genetic disorders and cancer to extensive surgical procedures. In developed countries, the blood supply is generally adequate. However, the projected decline in blood donor availability due to population ageing and the difficulty in finding rare blood types for alloimmunized patients indicate a need for alternative red blood cell (RBC) transfusion products. Increasing kno ...[more]

PMID: 22644674

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Project description: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.

Project description:: A depleted ?-cell mass causes diabetes complications that cannot be avoided by insulin administration. ?-Cell replacement can stop their development when restoring insulin's homeostatic role. This requires a sufficient number and an adequate functional state of the ? cells, together defined as "functional ?-cell mass." Intraportal implants of human pancreatic islet cells correct hyperglycemia in patients with type 1 diabetes, but this effect is transient and often incomplete. Studies to improve outcome are hindered by shortage in donor pancreases. Human pluripotent stem cells are a candidate source for mass production of grafts for ?-cell replacement. Their in vitro differentiation to pancreatic endoderm (stage 4) and to ?-cell-containing preparations (stage 7) provides grafts that generate ?-cell implants in mice. In vivo markers indicated a better outcome of device-encapsulated stage 4 cells and microencapsulated stage 7 cells as compared with nonencapsulated grafts. Encapsulation also offers the advantage of representative implant retrieval for direct analysis by ex vivo markers. Combination of in vitro, in vivo, and ex vivo markers allows comparison of different stem cell-derived grafts and implants, with each other and with clinical islet cell preparations that serve as reference. Data in mice provide insights into the biology of stem cell-generated ?-cell implants, in particular their capacity to establish and sustain a functional ?-cell mass. They can thus be indicative for translation of a graft to similar studies in patients, where metabolic benefit will be an additional marker of primordial importance.Human stem cell-derived preparations can generate insulin-producing implants in immune-incompetent mice. Steps are undertaken for translation to patients with type 1 diabetes. Their therapeutic significance will depend on their capacity to establish a functional ?-cell mass that provides metabolic benefit. This study proposes the combined use of in vitro, in vivo, and ex vivo markers to assess this potential in preclinical models and in clinical studies.

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Concise review: stem cell-derived erythrocytes as upcoming players in blood transfusion.

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Concise review: stem cell-derived erythrocytes as upcoming players in blood transfusion.

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