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How nanotubes can increase the number of blood stem cells

Electron microscopy image of hematopoietic stem/progenitor cell on top of nanostraws. Image credit: M. Hjort and L. Schmiderer
Electron microscope image showing a blood stem cell on top of a membrane with nanotubes. Photo: M. Hjort and L. Schmiderer

A multidisciplinary research team at Lund University has innovatively tackled what has long been a major problem in stem cell research. The project has now been awarded a Proof of Concept grant from the European Research Council, ERC.

Jonas Larsson, Professor of Molecular Medicine, and his research colleague Ludwig Schmiderer, together with Martin Hjort, researcher at NanoLund, have developed the method of using nanotechnology to propagate blood stem cells for stem cell transplantation.

“We have built a carpet of microscopic nanotubes. When the blood stem cell lands on the mat, the tubes form a channel through the cell surface, where the molecules we want to add to the cell can enter”, explains Martin Hjort.

To deliver molecules into cells, the main methods used today are strong electric fields that tear open holes in the cell membrane or genetically modified viruses that seek out the cell and enter it to deliver the molecules. But these methods have side effects in the form of increased cell death and the risk of serious genetic changes.

To make the process clinically viable, we had to invent a transfer method that is gentle on the cell.

“In our previous studies from a recently completed ERC project, we have been able to identify a number of gene-regulating RNAi molecules that are very potent and greatly enhance the growth of blood stem cells. Obviously, we want to exploit these molecules to make stem cells multiply more efficiently before transplantation. But to make the process clinically viable, we had to invent a transfer method that is gentle on the cell. That’s where nanotechnology comes in,” says Jonas Larsson.

Photo of three men.
From left: Ludwig Schmiderer, Jonas Larsson, Martin Hjort. Photo: Åsa Hansdotter

Under the carpet of nanotubes, are the RNAi molecules that the researchers want to bring into the cell. Using a weak electrical impulse, which does not adversely affect the cell, the molecules are charged into the blood stem cell through the tube that perforated the cell surface when the cell landed on the mat.  

Sometimes there are no suitable donors or not enough stem cells are produced to give all patients with leukemia or hereditary blood diseases the transplant that can save their lives. So, to grow blood stem cells, they are harvested – from umbilical cord blood after childbirth, for example – and multiplied in the laboratory. But blood stem cells are delicate and new technology is needed to grow them effectively. The global market value of blood stem cell transplantation has been estimated at over SEK 50 billion, so the research project has great potential for innovation:

A step forward to better treatment for leukemia and hereditary blood diseases

“It is incredibly exciting to combine nanotechnology with stem cell biology to develop a method that can solve the problem of delivering therapeutic molecules into the cell without harming it. Receiving an ERC grant for this interdisciplinary concept is a step towards a new and more effective treatment for leukemia and hereditary blood diseases,” concludes Jonas Larsson. 

The ERC’s mission is to encourage the highest quality research in Europe through competitive funding and to support investigator-driven frontier research across all fields, on the basis of scientific excellence. ERC Proof of Concept gives frontier research projects who already received ERC grants the chance to explore the commercial or societal potential of their work.

ERC project: RNable: RNA and Nanotechnology Enable Wider Accessibility to Stem Cell Transplantation

ERC news item “€25 million to edge frontier research closer to market”