Engineered macrophages to improve in vitro red blood cell maturation
Activation of a key transcription factor in stem cell-derived macrophages improves enucleation of surrounding red blood cells in vitro.
- In vitro RBC production
- Modelling erythropoiesis
- In vitro validation
- PCT/GB2019/051060 with priority date 13/04/2018
- Licensing and/or collaborative research
Blood transfusions are essential in treating traumatic emergency situations, as well as chronic hematological disorders. As a result, blood banks and transfusions services have a perpetual struggle with the supply of blood which also pose risks of infection and immune incompatibility.
To combat these problems production of artificial blood in the lab has garnered much interest. In particular, production of red blood cells (RBCs) is being assessed for use clinically. RBCs are generated naturally through erythropoiesis from blood stem cells, where the final stage of RBC maturation is to eject its nucleus, known as enucleation. This process is what researchers are trying to mimic in the lab. However, until now, efficient and full maturation and enucleation of stem cell-derived RBCs has not been possible.
Our researchers have successfully generated the erythroblastic island in vitro by genetically engineering stem cell-derived macrophages. The EI is an essential niche for red blood cell maturation and enucleation. When progenitor blood cells from umbilical cord or pluripotent stem cells are co-cultured with these engineered macrophages within the island, their maturation is significant improved and, crucially, enucleation efficiency is increased.
The artificial erythroblastic islands generated with this novel technique can be used to model erythropoiesis in vitro for research, as well as promoting the maturation of lab grown RBCs for potential use clinically. By improving the physiological relevance of the culture niche, our researchers have enhanced in vitro RBC generation, as well was identified key cytokines that can further augment RBC maturation and enucleation.
- Physiological relevant niche in vitro
- Improved enucleation yield from stem cell-derived RBCs
- Modelling of human erythropoiesis in vitro
- Identification of key cytokines for RBC maturation
Lopez-Yrigoyen et al., (2019). Nature Communications; and
Lopez-Yrigoyen et al., (2018). Experimental Hematology
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