How nanostraws can increase number of blood stem cells

Electron microscope image shows a blod stem cell on top of a membrane of nanotubes (Image: M. Hjort and L. Schmiderer)

Electron microscope image shows a blod stem cell on top of a membrane of nanotubes (Image: M. Hjort and L. Schmiderer)

An interdisciplinary research team has successfully used innovation to solve a persistent major problem in stem cell research. Namely, to gently introduce therapeutic biomolecules into target cells to increase their growth. The project has now been awarded the ‟Proof of Concept” grant by the European Research Council (ERC).

Jonas Larsson, professor of molecular medicine, and his research colleague Ludwig Schmiderer, together with Martin Hjort, researcher at Lund University, have developed a method using nanotechnology to multiply blood stem cells before a stem cell transplant.

‟We built a layer of microscopic nanostraws. When the blood stem cells land on the membrane, the straws form a channel through the cell surface, enabling us to introduce the molecules we want into the cell”, explains Martin Hjort.

To enable the delivery of molecules into cells, the current method mainly uses strong electrical fields which tear holes in the cell membrane, or genetically modified viruses that seek out the cell and penetrate it to release the molecules. However, these methods have side-effects in the form of increased cell mortality and the risk of serious genetic changes.

‟In our previous studies from a recently completed ERC project, we succeeded in identifying a number of gene-regulating RNAi molecules that are very potent and cause a significant increase in the growth of blood stem cells. Of course, we want to utilise these molecules to get the stem cells to multiply more effectively prior to a transplant. However, in order to make the process clinically sustainable, we had to invent a transfer method which is gentle on the cell. That is where nanotechnology comes in”, says Jonas Larsson.

Ludwig Schmiderer, Jonas Larsson, Martin Hjort (Photo: Åsa Hansdotter)

Ludwig Schmiderer, Jonas Larsson, Martin Hjort (Photo: Åsa Hansdotter)

Under the layer of nanostraws are the RNAi molecules that the researchers want to introduce into the cell. Using a weak electric impulse, which does not negatively impact the cell, the molecules are loaded into the blood stem cell through the tube that perforated the cell surface when the cell landed on the membrane.

Sometimes there are no suitable donors or the number of stem cells obtained is insufficient to enable all patients with leukaemia or hereditary blood diseases to get the transplant that could save their lives. Blood stem cells are therefore saved for cultivation – from umbilical cord blood after delivery for example – and multiplied in the laboratory. However, blood stem cells are sensitive and new technology is needed to enable them to be cultivated efficiently. The global market value for blood stem cell transplantation has been estimated to exceed SEK 50 billion, so the research project has major innovation potential:

‟It is incredibly exciting to combine nanotechnology with stem cell biology to develop a method capable of solving the problem of delivering therapeutic molecules into the cell without damaging it. Obtaining the ERC grant for this interdisciplinary concept is one step on the path to a new and more effective treatment for leukaemia and hereditary blood diseases”, concludes Jonas Larsson.

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