Thrombocytopenic disorders include numerous causes of decreased platelet production or increased platelet destruction. Having too few platelets can lead to internal or serious bleeding after surgery or injuries. Recent studies have shown that a drug called eltrombopag increases the production of platelets, but it has not benefited all patients. Now, researchers report a new miniature 3D model of human bone marrow that can help predict which patients will benefit from therapy.

The new 3D bone marrow model and the researchers’ findings are published in the journal eLife in a paper titled, “Miniaturized 3D bone marrow tissue model to assess response to Thrombopoietin-receptor agonists in patients.”

“Thrombocytopenic disorders have been treated with the thrombopoietin-receptor agonist eltrombopag,” wrote the researchers. “Patients with the same apparent form of thrombocytopenia may respond differently to the treatment. We describe a miniaturized bone marrow tissue model that provides a screening bioreactor for personalized, pre-treatment response prediction to eltrombopag for individual patients. Using silk fibroin, a 3D bone marrow niche was developed that reproduces platelet biogenesis.”

The researchers developed a mini 3D model of human bone marrow that combines a scaffolding of silk protein and culture of patient-derived cells to recreate the human bone marrow environment where platelets are produced. “This device is a significant improvement over previous models, requiring only a very small sample of blood to recreate platelet production,” explained first author Christian Di Buduo, PhD, research assistant professor at the department of molecular medicine, University of Pavia, Italy.

When the researchers added eltrombopag to a blood sample from a patient with a platelet disorder that had previously been treated with the drug, they observed that the number of platelets produced in the model corresponded to how each patient had responded to treatment with the drug.

Their new model may pave the way for personalized treatment for platelet disorders.

“Combining patient-derived cells and iPSCs with the 3D bone marrow model technology allows having a reproducible system for studying drug mechanisms and for individualized, pre-treatment selection of effective therapy in inherited thrombocytopenias,” wrote the researchers.

“This easy-to-reproduce system may also help scientists better understand what goes wrong in these disorders and how treatments work, as well as provide them with a new tool for testing new drugs that may lead to improved therapies in the future,” concluded senior author Alessandra Balduini, MD, principal investigator and professor at the University of Pavia.

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