Scientists successfully generate human platelets using next-generation bioreactor

Bioreactor-on-a-chip could help meet growing need for blood transfusions worldwide

2014-07-21

(Press-News.org) Boston, MA – Scientists at Brigham and Women's Hospital (BWH) have developed a scalable, next-generation platelet bioreactor to generate fully functional human platelets in vitro. The work is a major biomedical advancement that will help address blood transfusion needs worldwide.

The study is published July 21, 2014 in Blood.

"The ability to generate an alternative source of functional human platelets with virtually no disease transmission represents a paradigm shift in how we collect platelets that may allow us meet the growing need for blood transfusions," said Jonathan Thon, PhD, Division of Hematology, BWH Department of Medicine, lead study author.

According to the researchers, more than 2.17 million platelet units from donors are transfused yearly in the United States to treat patients undergoing chemotherapy, organ transplantation and surgery, as well as for those needing blood transfusions following a major trauma. However, increasing demand; a limited five-day shelf-life; and risk of contamination, rejection and infection have made blood platelet shortages common.

"Bioreactor-derived platelets theoretically have several advantages over conventional, donor-derived platelets in terms of safety and resource utilization," said William Savage, MD, PhD, medical director, Kraft Family Blood Donor Center at Dana Farber Cancer Institute/Brigham and Women's Hospital, who did not contribute to the study. "A major factor that has limited our ability to compare bioreactor platelets to donor platelets is the inefficiency of growing platelets, a problem that slows progress of clinical research. This study addresses that gap, while contributing to our understanding of platelet biology at the same time."

Blood cells, such as platelets, are made in bone marrow. The bioreactor—a device that mimics a biological environment to carry out a reaction on an industrial scale—uses biologically inspired engineering to fully integrate the major components of bone marrow, modeling both its composition and blood flow characteristics. The microfluidic platelet bioreactor recapitulates features such as bone marrow stiffness, extracellular matrix composition, micro-channel size, and blood flow stability under high-resolution live-cell microscopy to make human platelets.

Application of shear forces of blood flow in the bioreactor triggered a dramatic increase in platelet initiation from 10 percent to 90 percent, leading to functional human platelets.

"By being able to develop a device that successfully models bone marrow represents a crucial bridge connecting our understanding of the physiological triggers of platelet formation to support drug development and scale platelet production," said senior study author Joseph Italiano, Jr., PhD, Division of Hematology, BWH Department of Medicine, and the Vascular Biology Program at Boston Children's Hospital.

In terms of next steps, the researchers would like to commence phase 0/I in human clinical trials in 2017.

"The regulatory bar is appropriately set high for blood products, and it is important to us that we show platelet quality, function and safety over these next three years since we'll likely be recipients of these platelets ourselves at some point," said Thon.

INFORMATION: This research was supported by the National Institutes of Health (R01Hl68130), American Society of Hematology Scholar Award, Brigham Research Institute at Brigham and Women's Hospital, and Marie Curie Actions International Outgoing Fellowship (300121).

Jonathan Thon, PhD, and Joseph Italiano, Jr., PhD are both founders of Platelet BioGenesis, a company that aims to produce donor-independent human platelets from human-induced pluripotent stem cells at scale.

Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in Massachusetts and employs nearly 15,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Brigham Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, more than 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $650 million in funding. For the last 25 years, BWH ranked second in research funding from the National Institutes of Health (NIH) among independent hospitals. BWH continually pushes the boundaries of medicine, including building on its legacy in transplantation by performing a partial face transplant in 2009 and the nation's first full face transplant in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative. For more information, resources and to follow us on social media, please visit BWH's online newsroom.

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Scientists successfully generate human platelets using next-generation bioreactor

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