Platelets on demand
OUR FACULTY | Platelets are an expensive biomedical commodity. These microscopic cells, which come to the rescue when our blood vessels need to be repaired, cannot be frozen. They are stable for only three to five days at room temperature. Donated natural platelets are often in short supply, and their use comes with the risk of disease transmission.
But researchers from the University of Delaware have shed new light on the mechanism of platelet formation, paving the way to accelerate and enhance their production using stem cells.
A paper detailing the breakthrough appeared as the cover story in the journal Blood last September, and a provisional patent application has been filed on the process.
Ironically, a key factor in the team’s success was exploiting what was previously viewed as “cell junk.”
Lead author Terry Papoutsakis, the Unidel Eugene du Pont Chair of Chemical and Biomolecular Engineering, explained that platelets are produced by megakaryocytes, large cells in the bone marrow whose microparticles were “until recently viewed as inconsequential cell debris.”
“We now know that they play a significant biological role in platelet formation,” Papoutsakis added.
He and his research team found the enhanced generation of pre-platelets and platelet-like particles under shear stress correlated with physiological observations—in healthy adults, both acute and prolonged exercise leads to elevated platelet counts.
Now, Papoutsakis and his team are using these findings to design and develop the technologies to produce platelets on demand. This bioreactor technology is at the core of the University’s patent, which would produce platelets, pre-platelets, platelet-like particles and megakaryocyte microparticles for transfusion medicine, using stem cells as starting material.
Unlike platelets themselves, the microparticles can be frozen, which will enable them to be stored and then used for production of platelets on an as-needed basis.
“Knowing that these microparticles have a biological function opens the door to other applications, including genetic therapies,” Papoutsakis says. He credits UD doctoral student Jinlin Jiang, EG16PhD, with the breakthrough.
Reviewers of the paper, titled “Shear Enhances Thrombopoiesis and Formation of Microparticles that Induce Megakaryocytic Differentiation of Stem Cells,” referred to the findings as “very exciting,” “highly novel” and even “game changing.”
The paper was co-authored by Jiang and Donna Woulfe, assistant professor in the Department of Biological Sciences.
Jiang and Chen-Yuan Kao, EG20PhD, also a doctoral candidate in chemical and biomolecular engineering, are co-inventors on the patent.
The Papoutsakis lab at the Delaware Biotechnology Institute focuses on systems biology, metabolic engineering and experimental and computational genomics with applications in stem-cell biology and prokaryotic biology.
“The incidence of a disease known as ITP, which stands for idiopathic thrombocytopenic purpura, is on the rise,” says Papoutsakis. “ITP is a bleeding disorder in which the immune system destroys platelets. We’re hopeful that our discovery can break the vicious cycle of this disease as well as other conditions that cause reduced platelet count and cause life-threatening bleeding.”
Article by Diane Kukich, AS73, 84M
