Engineering blood: Making Platelets in the Lab

Blood transfusions are of growing importance as every two seconds someone in the United States needs blood.  In just one car accident a victim could need as much as 100 pints of blood. One part of the blood that is often transfused is the platelets. Of the 1.6 million people who were diagnosed with cancer last year, many of them have low platelet counts due to chemotherapy or radiation. These patients rely on platelet transfusions on a regular basis.

 

Platelets are cell fragments that are produced in the bone marrow from parent cells called megakaryocytes. The outer edges of megakaryocytes extend through the endothelium where parts of their cytoplasm turns into turn into disk-like extensions that become platelets. When someone gets a cut or injury, platelets are the first cells to respond and help the blood clot, preventing further blood loss. The process of blood clotting occurs through a coagulation cascade that includes many different enzymes. The steps of hemostasis, or the process to stop bleeding, are vasoconstriction in which blood flow to the injury site is decreased, temporary blockage of the break, and then finally coagulation, or the formation of a clot to seal the hole into the tissue can be repaired. This process of clot formation is an example of a positive feedback loop. As more and more platelets aggregate, they recruit other platelets to do the same. Additionally, platelets will work in conjunction with white blood cells from the immune system to repair the wound. Platelets can store and release chemokines and cytokines (as seen in the image below), allowing them to interact with immune system cells in order to respond to inflammation.

Created by Jodi Forward

Recently, scientists at Brigham and Women’s Hospital in Boston engineered a source of human blood without the need for a human donor. The scientists developed a platelet bioreactor that can make functional human platelets in vitro. According to the researchers, donors provide more than 2.17 million platelet units each year in the United States to give blood transfusions for major trauma victims as well as for those undergoing chemotherapy, organ transplantation and surgery. However, the demand for blood is increasing and the number of donors is not enough to keep up with that demand.

Making platelets has proven difficult in the past, but through biological engineering techniques, the scientists were able to successfully produce platelets. By mimicking the biological environment of the bone marrow, the bioreactor has shown to successfully make platelets at a high rate. They were able to recreate bone marrow stiffness, extracellular matrix composition, and blood flow stability. When the scientists applied shear forces in the bioreactor that are similar to the blood flow platelets face in vivo, the initiation of platelet production increased from 10 percent to 90 percent.

American Society of Hematology. Digital Image. http://www.hematology.org. Accessed March 2015.

The use of a bioreactor to make platelets has many advantages over human donors. When blood transfusions come from human donors, there is a risk of contamination or rejection. By creating the technology to make platelets in a lab, these risks can be minimized. With no disease transmission dangers, the platelets created by this bioreactor have the potential to transform the way blood is transfused around the world. In addition, platelets only have a five-day shelf life, preventing the possibility of storing donated platelets for long periods of time. The bioreactor allows for the production of platelets on an industrial scale. In the future, the researchers would like to determine the success of these platelets in a human clinical trial so that they could be considered an alternative source for platelet transfusions.

Ref:

American Cancer Society: http://www.cancer.org

American Red Cross: http://www.redcrossblood.org/learn-about-blood/blood-facts-and-statistics

Thon JN, Maxutis L, Wu S, Sylman JL, Ehrlicher A, Machlus KR, Feng Q, Lu S, Lanza R, 

      Neeves KB, Weitz DA, and Italiano Jr JE. Platelet bioreactor-on-a-chip. Blood, 124:(12) 1857-

      66 (2014).