Most people recover from cuts and gashes easily and without profuse bleeding. They can thank their platelets, blood cells that bind together when they encounter damaged blood vessels. The coagulation plugs the wound and helps damaged vessels heal by releasing growth factors.

But some patients recovering from injuries, surgeries, or receiving chemotherapy can have dangerously low platelet counts, which puts them at risk of heavy bleeding. These patients need platelet transfusions, but so far these cells could only be harvested from human donors, which have resulted in a widespread platelet shortage.

Unfortunately, platelets can’t be frozen and must be kept at room temperature, where bacteria in blood quickly multiplies and destroys the samples. As a result, platelets have a shelf life of no more than five days and can’t be stocked up in advance. Natural disasters, weather flukes and even vacation seasons result in unexpected donation drops.

Platelet BioGenesis is working to solve those problems. The Cambridge, Mass.-based maker of human platelets has built a device that mimics the physiology and conditions under which platelets are normally created within the human body.

“The (current) system depends on volunteer donors, and because there’s already not enough people donating blood, on cold or rainy days the system is operating at the level of crisis,” says Jonathan Thon, CEO and co-founder of the company. “The availability drops, surgeries need to be postponed, and patients receive fewer platelets than they need.”

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In the human body, platelets are generated by large bone marrow cells called megakaryocytes. The megakaryocytes extend their “arms,” called proplatelets, through the skin cells that line the blood vessels. The platelets separate from the end of the arms and enter the blood stream, while the megakaryocytes continue to produce them until depleted. To produce platelets, those arms must experience the shear pressures of their environment. In other words, they must feel the blood flow.

Biogenesis replicates that process in two stages. By using specific growth factors, the company converts commercially available induced human pluripotent stem cells into megakaryocytes. Then, using a specialty bioreactor, the company imitates the physical environment to help megakaryocytes create platelets.

The bioreactor consists of two chambers, top and bottom, separated by a porous membrane. The idea is to mimic the human body’s physiology: The top chamber acts as the bone marrow, the bottom as a blood vessel, and the porous membrane as the skin cell lining. In the top chamber, megakaryocytes gather along the porous membrane, evenly distributed along the entire length and width of the device so they all experience the same shear stress no matter where they are. As the fluid flow is passed through the bioreactor, the shear pressures prompt them to extend their arms into the lower chamber through the porous membrane—and begin to release platelets, which are then harvested.

“By giving these stem cells the appropriate stimuli at the appropriate points of their differentiation we drive them to naturally differentiate toward the cells we are trying to create,” Thon says, adding that the even distribution of megakaryocytes was a tremendous engineering challenge the team had to master.

The bioreactor-made platelets are identical to the human ones. By removing the volunteer donor from the equation, the company aims to build a steady supply of the cells. “There are roughly two million platelet transfusions every year in the U.S.,” says the company’s president Sven Karlsson, adding that with the current cost of about $1,000 per unit there’s a pressing need for a stronger, more consistent supply.

The company’s immediate goal is to scale up the platelet production to reduce the continuous critical shortage and eventually eliminate it. The human clinical trials for this phase are planned to start in 2020.

For the second stage, the company plans to make custom platelets for drug delivery in cancer patients.

Platelets are effective in that application because they carry growth factors in their secretory granules that are normally used to heal blood vessels. Tumors attract platelets and rely on their growth factors to expand. As a result, tumors can be platelets’ natural targets. If researchers load the platelets with cancer-killing medicines instead of growth factors platelets, the cells can deliver drugs more precisely than regular chemotherapy, in which only five to ten percent of the drugs actually reach tumors. The rest end up in other parts of the body, damaging healthy organs and tissues. Those designer platelets can be “prebuilt” with the chemotherapy drugs already in them.

“We can genetically engineer stem cells to produce and package the drugs into platelets,” Thon says, adding that the company hopes this second phase will go to human trials sometime in the 2020s. “So megakaryocytes become little drug factories.”

Lina Zeldovich is a freelance technology writer.

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