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Blood Formation: Researchers Engineer Human Bone Marrow Tissue

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Researchers have developed an artificial tissue inwhich human blood stem cells remain functional fora prolonged period of time. Scientists from the University of Basel, University Hospital Basel, and ETHZurich have reported their findings in the scientificjournal PNAS.

Every day in the bone marrow several billion bloodcells are formed. This constant supply is ensured byblood stem cells located in special niches within themarrow. These stem cells can multiply and matureinto red and white blood cells, which then leave thebone marrow and enter the bloodstream.

For several years, researchers have been trying toreproduce natural bone marrow in the laboratory inorder to better understand the mechanisms of bloodformation and to develop new therapies – such as forthe treatment of leukaemia.

However, this has proven to be extremely difficult because – in conventional in vitro models – the bloodstem cells lose their ability to multiply and to differentiate into different types of blood cells.

A new kind of artificial bone marrow

Now, researchers have engineered an artificial bonemarrow niche, in which the stem and progenitor cellsare able to multiply for a period of several days.These findings were reported by researchers working under Professor Ivan Martin from the Departmentof Biomedicine at the University of Basel and University Hospital Basel and Professor Timm Schroederfrom ETH Zurich’s Department of Biosystems Science and Engineering.

The researchers have developed an artificial tissuethat mimics some of the complex biological properties of natural bone marrow niches. To do this, they combined human mesenchymal stromal cells with aporous, bone-like 3D scaffold made of a ceramic material in what is known as a perfusion bioreactor,which was used to combine biological and synthetic materials.

This gave rise to a structure covered with a stromal extracellular matrix embedding blood cells. In thisrespect, the artificial tissue had a very similar molecular structure to natural bone marrow niches, creating an environment in which the functionality ofhematopoietic stem and progenitor cells could largelybe maintained.

A tool for personalised research

The new technique could also be used to produce tailor-made bone marrow niches that have specific molecular properties and that allow the selective incorporation or removal of individual proteins.

This opens up a whole host of possibilities, from researching factors that influence blood formation inhumans, to drug screening with a view to predicting how individual patients will respond to a certaintreatment.

“We could use bone and bone marrow cells from patients to create an in vitro model of blood diseasessuch as leukaemia, for example. Importantly, wecould do this in an environment that consists exclusively of human cells and which incorporates conditions tailored to the specific individual,” explain IvanMartin and Timm Schroeder.

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