14 January 2014

Bone marrow in a test tube

Artificial bone marrow has been created for the cultivation of stem cells

NanoNewsNet based on Karlsruhe Institute of Technology: KIT Researchers Develop Artificial Bone MarrowArtificial bone marrow can be used to grow hematopoietic stem cells, and its prototype has just been developed by scientists from the Karlsruhe Institute of Technology (Karlsruher Institut fur Technologie, KIT), the Max Planck Institute for Intelligent Systems, Stuttgart, and the University of Tubingen (Eberhard Karls Universitat Tubingen).

The porous structure created by them possesses key properties of natural bone marrow and can be used for reproduction of stem cells in laboratory conditions. In the future, this development will help save lives and restore health to hundreds of thousands of leukemia patients.


Stem cells (yellow-green) in the substrate structure (blue),
serving as the basis of artificial bone marrow. Photo: S. Lee-Thedieck/KIT.

The researchers report the results of their study in the journal Biomaterials (Raic et al., Biomimetic macroporous PEG hydrogels as 3D scaffolds for the multiplication of human hematopoietic stem and progenitor cells).

Blood cells, such as erythrocytes or leukocytes, are constantly being replaced by new, formed hematopoietic stem cells (HSCs) located in specialized niches in the bone marrow. Hematopoietic stem cells are used to treat blood diseases such as leukemia. This method of treating leukemia consists in replacing the affected patient's cells with healthy hematopoietic stem cells from a suitable donor.

However, due to the lack of immunologically compatible donors and, consequently, transplant material, this method does not allow to cure all patients with leukemia. And although the problem can be solved by reproducing hematopoietic stem cells, until now this has remained impossible, since cells of this type retain stem properties only in the natural environment, that is, in their native niche in the bone marrow. Outside of this niche, their properties change. Therefore, stem cell reproduction requires an environment close to the niche of stem cells in the bone marrow.

The stem cell niche is a complex microenvironment with specific properties. The areas of the bone in which such niches are located are very porous and resemble a sponge. In this three-dimensional environment there are not only bone and hematopoietic stem cells, but also cells of other types that exchange signaling substances with HSC. In addition, the space between the cells is filled with a matrix that guarantees a certain stability and provides the cells with anchor points. Being in the niche of stem cells, these cells are also supplied with nutrients and oxygen.

Dr. Cornelia Lee-Thedieck and her colleagues from several leading research centers in Germany artificially reproduced the basic properties of natural bone marrow in the laboratory. With the help of synthetic polymers, scientists have created a porous structure that mimics the spongy substance of bone in the area of the hematopoietic bone marrow. In addition, they added protein building blocks similar to those existing in the bone marrow matrix so that the cells had anchor points, and to ensure metabolism, they introduced other types of cells from the stem cell niche into the structure.


A synthetic structure imitating bone marrow is placed with tweezers
into a vessel for growing stem cells. Photo: S. Lee-Thedieck/KIT

The researchers then injected hematopoietic stem cells isolated from umbilical cord blood into this artificial bone marrow. The subsequent reproduction of these cells took several days. Analyses carried out by various methods have shown that HSCs are indeed reproduced in an artificially created environment. In comparison with standard methods of cultivation, a larger number of stem cells retain their specific properties in artificial bone marrow.

So far, artificial bone marrow, which has the basic properties of natural, will be used for a detailed study of the interaction of materials and stem cells. This information will help to find out how it is possible to influence the behavior of stem cells using synthetic polymers. As for the creation of an artificial niche of stem cells for the cultivation of hematopoietic stem cells for the treatment of leukemia, according to German scientists, it will take ten to fifteen years.

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