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International collaboration will advance understanding of how red blood cells are generated

University of Illinois Chicago College of Engineering BIOE professor Zhangli Peng (L) and Dr. Peng Ji, Vice Chair of Research and Professor of Pathology at Northwestern, collaborate on a red blood cells project.

Richard and Loan Hill Department of Biomedical Engineering Assistant Professor Zhangli Peng has received a three-year National Science Foundation (NSF) grant titled “Mechanisms of Terminal Erythroid Enucleation.” As the Principal Investigator, the $600,000 and €251,200 project will help Peng and his collaborative research team to better understand how red blood cells are generated through the process of erythropoiesis.

This collaborative research effort will be done with Co-PI and Northwestern University Professor of Experimental Pathology and Hematopathology Peng Ji, MD, PhD, and Co-PI Aix Marseille University French National Center for Scientific Research researcher Emmanuèle Helfer through the jointed funding between NSF and French Agence Nationale de la Recherche (ANR).

As the first study of its kind, this project aims to advance fundamental understanding of enucleation of erythroid, a precursor of red blood cells, a process unique to mammals, and provide new knowledge to improve in vitro red blood cell production for blood supply and therapeutic purposes. The removal of the nucleus, or enucleation, allows more space inside of red blood cells for hemoglobin, the protein in red blood cells that is responsible for the delivery of oxygen to tissues. But the efficiency of enucleation during in vitro cell culturing is much lower than inside the bone marrow.

Peng and his team aim to understand and improve the enucleation process in controlled microfluidic devices mimicking bone marrow.

Co-PI Aix Marseille University French National Center for Scientific Research researcher Emmanuèle Helfer

In doing so, Peng and his team hope to facilitate this process to enhance the efficiency of artificially producing blood. The supply of blood in hospitals is heavily dependent upon donation. With the recent increased demand of blood products, especially during the Covid-19 pandemic, artificially producing blood will ensure that all patients can receive a blood donation, even with rare blood types. Artificially produced blood can also be used as a therapeutic carrier by adding therapeutic proteins on or inside the red blood cell membranes to produced engineered red blood cells.

As the study began in April 2023, PhD and post-doctoral students from UIC, Northwester, and Aix Marseille University will visit each other to design and fabricate an in vitro microfluidic device to mimic the microenvironment of bone marrow with extremely small inter-endothelial gaps that allows live imaging of enucleation. This will provide a similar mechanical environment to facilitate the process of enucleation to enhance the efficiency of artificially producing blood.

The knowledge obtained from this project will help overcome the bottleneck of in vitro enucleation, which could potentially revolutionize the industry of blood supply.