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Synthetic Bone Marrow System Produces Platelets

Alessandra Balduini

Alessandra Balduini (alessandrabalduini.com)

19 February 2015. Bioengineers in the U.S. and Italy designed a programmable bioreactor system that emulates bone marrow to produce platelets, blood cells that coagulate to prevent bleeding. The team led by Tufts University bioengineering professors Alessandra Balduini and David Kaplan published its findings last month in the journal Blood (paid subscription required).

Balduini and Kaplan, with colleagues from Tufts in Medford, Massachusetts and University of Pavia in Italy developed a three-dimensional environment that produces platelets in the lab, but the system can also be programmed to test new therapies for blood-related diseases instead of using animals. Platelets are cells in the blood whose function is to stop bleeding from broken blood vessels.

When platelets in the blood are working properly and at normal levels, they respond to signals of a damaged blood vessel from a protein known as thrombin and accumulate at the site forming a clot, which slows the blood flow. The clot forms by platelets depositing a natural polymer called fibrin at the point of damage, which changes the shape of the platelets and lets them clump together in a clot to staunch the blood flow.

Platelets and other blood cells are produced in marrow, the spongy substance in bones, which the Tufts/Pavia system simulates to produce platelets on demand. The system is made from a porous silk sponge providing a biocompatible environment that acts as a reactor, culturing an individual’s own stem and progenitor cells into bone marrow cells, known as megakaryocytes, as well as the supporting endothelial cells. Inside the silk sponge is a microvascular system made from silk and collagen, with proteins that bind the materials together into tiny tubes.

The Tufts/Pavia team tested the reactor system, which produces millions of platelets, although the output per bone marrow cell is lower than normally made by the body. Nonetheless, platelets produced by the system show they aggregate and clot like normal platelets. The system, say the authors, is scalable that makes it possible to generate larger numbers of platelets as needed, which reduces the need to store platelets for later use.

In addition, the bioreactor can be programmed to alter platelets’ characteristics, such as mechanical properties, binding of signaling proteins, and components. This programming ability enables the system to produce platelets resembling those with different diseases, thus offering a platform to test therapies for platelet-related disorders.

“There are many diseases where platelet production or function is impaired,” says Balduini, who is on the faculty at both Tufts and Pavia, in a Tufts statement. “New insight into the formation of platelets would have a major impact on patients and health care.”

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