Cultured blood is the production of blood cells in the lab from stem cells or blood stem cells. Stem cells which can form any cell type in the body or blood stem cells which can form all types of blood are used as starting material which is grown and differentiated into specific cell types. It is possible to produce red blood cells and platelets in culture but a hurdle to overcome is in scaling up production to produce a standardized blood product for transfusion services . Combining blood culture and gene editing opens up the possibility of correcting genetic defects in patients with blood disorders and growing functional blood cells for these patients .
Red Blood Cells
Red blood cells carry oxygen to body tissues and carry carbon dioxide away . The aim of using tissue engineering to culture red blood cells would be to replace the need for blood donors and have an unlimited source of infection-free red blood cells ready for patients in need . Peripheral human stem cells (HSCs) that are positive for CD34, a glycosylated transmembrane protein, are blood cell progenitors that can differentiate into all blood cell types. A French research team lead by Luc Douay used these peripheral HSCs to derive red blood cells . After testing the maturation of these the cells in mice, they derived red blood cells from a patient’s own peripheral HSCs and put the cultured blood back in the patient where it stayed in circulation as long as native red blood cells .
A United Kingdom based research initiative called the Novosang project (previously BloodPharma project) was established in response to the US Defense Advanced Research Projects Agency (DARPA) seeking a method of producing blood on the battle field . While Novasang did not receive DARPA funding, it worked under UK funding to produce blood cells from human iPSCs from adult donors that are clinical grade with a Good Manufacturing Practice (GMP) protocol . Novosang is partnered with the Scottish National Blood Transfusion Service, NHS Blood and Transplant, several UK Universities and industry partner Roslin Cells .
Jan Frayne of the Novosang project and University of Bristol, UK, is one of the lead researchers of a paper describing immortalized erythroid lines of cells that can divide indefinitely and be induced to form red blood cells . They started with bone marrow cells that were CD34 positive and inserted the cancer gene, human papilloma virus (HPV) . Since mature red blood cells expel their nucleus, all DNA, including the HPV insert are not present in the final product. Filter systems would be needed to ensure cells with nuclei are not included in the final product.
George Daley’s lab in Boston differentiated human pluripotent stem cells (hPSCs) into haemogenic endothelium cells, and identified transcription factors or gene regulator proteins that turn these cells into haematopoetic stem and progenitor cells that can form all types of blood cells . Adult mouse endothelial cells have also been reprogrammed into mouse blood stem cells by researchers at Cornell University .
Platelets are tiny cell fragments lacking a nucleus, released from megakaryocytes in bone marrow, that are involved in blood clotting . Immortalized megakaryocyte progenitor lines have been grown from human induced pluripotent stem cells (iPSCs) derived from human skin by Koji Eto of Kyoto University, Japan . These iPSC-derived megakaryocytes were used to generate platelets.
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