proplatelets (green) that will
become mature platelets
Image from Tufts University
Researchers say they’ve developed a 3-dimensional system that reproduces the structure and physiology of human bone marrow.
Using this silk-based bone marrow niche tissue system, the team was able to manufacture functional human platelets.
The system might also prove useful for studying platelet-related diseases and predicting the efficacy of new drugs, according to the researchers, who said the new system could be a more precise and cheaper alternative to animal models.
“There are many diseases where platelet production or function is impaired,” said Alessandra Balduini, MD, of Tufts University in Medford, Massachusetts.
“New insight into the formation of platelets would have a major impact on patients and healthcare. In this tissue system, we can culture patient-derived megakaryocytes—the bone marrow cells that make platelets—and also endothelial cells, which are found in bone marrow and promote platelet production, to design patient-specific drug administration regimens.”
Dr Balduini and her colleagues described the system in Blood.
The system combined microtubes spun of silk, collagen, and fibronectin surrounded by a porous silk sponge. Megakaryocytes—some derived from patients—were seeded into the engineered microvasculature.
The researchers were able to increase platelet production in the bioreactor by embedding the silk with active endothelial cells and endothelial-related molecular proteins that support platelet formation.
The special properties of silk protein were essential to successfully mimicking the bone marrow microenvironment, said study author David Kaplan, PhD, of Tufts University.
“Silk protein possesses a unique molecular structure that enables it to be modeled in a wide variety of forms and stiffnesses, characteristics that have been shown to affect platelet formation and release,” Dr Kaplan said.
“Furthermore, silk is biocompatible and has the ability to stabilize bioactive agents at normal temperatures. Therefore, we can ‘functionalize’ it by adding such agents.”
In addition, the silk is nonactivating to platelets, which allowed the researchers to collect functional platelets from the bioreactor. Tests showed the platelets were able to aggregate and clot.
Although the number of platelets produced per megakaryocyte was lower than normally made in the body, the researchers said the system represents a significant advance over previous models. The scalable nature of the bioreactor system provides engineering options to increase the yield of platelets in ongoing studies.
In addition to providing a platform for studying the processes that regulate platelet production and related diseases, the researchers hope the platelets produced can be used as a source of growth factors for wound healing in regenerative medicine.
“The need for platelet production systems to treat patients with related diseases is significant,” Dr Kaplan said. “This patient-specific system could provide new insight and options for clinical treatments.”
“Further, the platelets can be generated on demand, avoiding the complications of storage problems, and in greater quantities and with better quality and control in terms of morphology and function.”
