Rising demand/constrained supply. A five-day shelf life. Risks of contamination, infection, and rejection. All these issues come to the fore when one contemplates the platelet supply, which is still entirely dependent on human donors. Unfortunately, alternative sources—platelets from bioreactors—have been plagued with inefficiencies, disappointing patients, clinicians, and researchers.
A new kind of bioreactor, however, may relieve worries over the platelet supply, which is so important to patients undergoing chemotherapy, organ transplantation, and surgery, as well as for those needing blood transfusions following a major trauma. This bioreactor is not a tank made of steel or plastic. Instead, it is a microfluidic chip.
The chip, fashioned by scientists at Brigham and Women’s Hospital (BWH), is designed to mimic bone marrow, the ultimate source of platelets. The scientists hope to use the chip to carry out platelet production on an industrial scale.
The scientists described their work in an article published July 21 in Blood, in an article entitled, “Platelet bioreactor-on-a-chip.” This article details how the chip integrates 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.
“Physiological shear stresses triggered proplatelet initiation, reproduced ex vivo bone marrow proplatelet production, and generated functional platelets,” wrote the authors. “Modeling human bone marrow composition and hemodynamics in vitro obviates risks associated with platelet procurement and storage to help meet growing transfusion needs.”
"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 to meet the growing need for blood transfusions," said Jonathan Thon, Ph.D., BWH Department of Medicine, lead study author.
Besides possibly addressing growing blood transfusion needs, bioreactor-sourced platelets could advance research. “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,” explained senior study author Joseph Italiano, Jr., Ph.D., BWH Department of Medicine, and the Vascular Biology Program at Boston Children's Hospital.
The researchers intend to start Phase 0/I 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," added Dr. Thon.