Assistant Professor Aga Khan University Karachi, Pakistan
Abstract: Blood transfusion is a critical component of modern medicine, yet the global demand for red blood cells (RBCs) continues to outpace supply, particularly in low- and middle-income countries. Developing reliable methods for the sustainable in vitro production of red blood cells is crucial to offering an alternative source of clinical-grade blood, especially for individuals with rare blood group phenotypes. Immortalized erythroid progenitor cell lines represent the most promising emerging technology to accomplish this objective. Current methods for in vitro generation of red cells from adult and bone marrow progenitors fail to provide a sustainable supply, and existing systems relying on pluripotent stem cells as progenitors cannot produce viable red cells. To address this challenge, we have adopted an alternative strategy by immortalizing early adult erythroblasts from cord blood hematopoietic stem cells to generate a stable cell line that provides a continuous supply of red cells. We have successfully generated immortalized erythroid progenitor cell lines derived from CD34+ hematopoietic stem cells (HSCs) derived from cord blood using lentiviral vectors to introduce HPV16 E6/E7 oncoproteins. By employing a three-stage erythroid culture system, these immortalized cells efficiently differentiate into mature, functional reticulocytes that can be isolated through filtration. Comprehensive characterization has shown no functional or molecular differences between these reticulocytes and in vitro-cultured adult reticulocytes, with no evidence of aberrant protein expression. This work establishes a viable method for producing red cells in vitro for clinical applications. This work represents a significant advancement in addressing blood shortages, offering a sustainable and scalable solution for transfusion-grade RBC production. The potential implications of this achievement extend beyond addressing transfusion demands, providing a platform for future research into erythroid biology and the development of personalized cellular therapies. Our findings demonstrate a promising pathway to revolutionize blood supply systems globally.
Funding Source: This work was funded by the Aga Khan University (AKU) University Research Council (URC) grant No. 191018CRM
