19 February 2015

A three-dimensional model of the bone marrow produces platelets

An international team of researchers working under the leadership of scientists from Tufts University (USA) and the University of Pavia (Italy) has developed a unique three-dimensional tissue system reproducing the complex structure and physiological parameters of human bone marrow. This system, using porous silk protein as a biological matrix, is capable of producing functional platelets potentially suitable for clinical use, and can also be used as a laboratory system for studying blood diseases and evaluating the effectiveness of experimental drugs.

Platelets can perform completely opposite roles in the body. They provide blood clotting, saving a person from blood loss with injuries of various kinds. At the same time, they play a pathological role in myocardial infarctions, strokes, inflammation and cancer. The formation of platelets, as well as other blood cells, occurs in the bone marrow, filling the cavities of spongy bones. In addition to hematopoietic cells, many cells of various types participate in the formation of the bone marrow microenvironment, including endothelial cells of blood vessels, as well as components of the extracellular matrix.

The ideal material for reproducing the microenvironment of the bone marrow turned out to be silk protein, the unique molecular structure of which allows you to create models whose shapes and densities vary widely, which is extremely important for the proper formation of platelets. Moreover, silk is biocompatible and has the ability to stabilize bioactive agents at normal temperatures. Silk is also neutral with respect to platelets, which eliminates the triggering of the thrombosis mechanism, providing the possibility of isolating functional platelets from the bioreactor.

The new system consists of microtubules woven from silk, collagen and fibronectin and surrounded by a porous spongy material made of silk protein. Platelet precursors – megakaryocytes – are introduced into this system, as well as active endothelial cells and proteins that support the platelet formation process.

In the new tissue system, platelet–producing cells are megakaryocytes (colored blue) –
release fiber-like platelet precursors (colored green),
subsequently turning into mature platelets.

Laboratory tests have shown that platelets formed in the system and isolated from it successfully form blood clots. Despite the fact that in the conditions of the system, one megakaryocyte forms much fewer platelets than in the body, the new bioreactor significantly exceeds all previous developments.

The developers hope that in addition to providing a platform for studying the processes regulating platelet formation and the development of disorders of this process, the new bioreactor in the future can be used to produce platelets suitable for clinical use, as well as growth factors that promote wound healing, including ulcers and burns, as well as stimulation of bone regeneration in dentistry and maxillofacial surgery.

Article by C. A. Di Buduo et al. Programmable 3D silk bone marrow niche for platelet generation ex vivo and modeling of megakaryopoiesis pathologies is published in the journal Blood.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Tufts University:
3-D Engineered Bone Marrow Makes Functioning Platelets


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