Emile van den Akker (PhD) – group leader, sanquin Research, department of Hematopoiesis

Extraordinary developments: Blood grown to order

Blood made to order, grown from stem cells: it might sound like science fiction, but for research group leader Emile van den Akker, it’s part of his daily work schedule. His Haematopoiesis research group at Sanquin Research is exploring ways of generating blood tailored to patients for whom it is difficult to find suitable donor blood. The research group is supported by a prestigious fund from ZonMw.

“Our technology for generating pluripotent stem cells can be really interesting for a range of companies”

Emile van den Akker is delighted: as part of ZonMw’s research programme Pluripotent Stem Cells for Inherited Diseases and Embryonic Research (PSIDER), a consortium of groups that includes his research group has received €2 million funding for the coming five years. The focus of Van den Akker’s group is on blood-forming stem cells. “Pluripotent stem cells are stem cells that can evolve into any type of cell in your body, depending on the trigger they receive,” he explains. “Therefore you could also let them develop into blood-forming stem cells. We call the blood-forming process haematopoiesis. And we have discovered a way of letting these pluripotent stem cells differentiate into blood cells in vitro, so outside of the body.”

Scaling up the growing process
This discovery opens the doors to creating healthy red blood cells, tailored to specific patients. The project’s aims are twofold: it both investigates possibilities for scaling up the growing process of red blood cells, and studies the maturation of pluripotent cells into blood-forming stem cells. In the future, these could be used, for example, to replace bone marrow transplants, during which patients receive donor stem cells – a process for which it is notoriously difficult to find the exactly matching donors. But Van den Akker sees even more possibilities for applying the technology: “You can also use the lab-grown blood as a carrier of certain therapeutic agents for the treatment of diseases,” he says.

First there is a major obstacle to surmount: scaling up the process of growing the blood cells. “At the moment, it is terribly expensive to generate even the tiniest amount of blood,” says Van den Akker. “250 ml costs between 300,000 and 400,000 euro. We are currently working with Delft University of Technology (TU Delft) to test bioreactors with a capacity of 1.5 to three litres. As part of a first clinical trial, we will transfuse six healthy volunteers with blood that we have generated in the bioreactors. We are using their own blood-forming stem cells as a basis for creating this blood – these stem cells are a step further in the process of development compared to pluripotent stem cells. But eventually, we want to be able to understand the preceding process of the maturation of pluripotent stem cells into blood-forming stem cells and then scale up in the bioreactors.”

“Together, we can achieve so much more”

The iPSC facility
Collaboration is an important element in successful research. The way Van den Akker and his colleagues collaborate with bioreactor experts in the field at TU Delft is a good example. “Combined with our expertise in growing cells, this produces a great synergy,” he says. “Together, we can achieve so much more. We also work with Erasmus MC and the UMC Utrecht to do research on various patient groups.” In addition, within the project, expertise in the field of blood-forming stem cells is assured by the group of Gerald de Haan, who has recently arrived at Sanquin from UMCG.

Van den Akker also foresees promising opportunities for collaboration with new parties in the Health and Innovation District. “Our technology for growing pluripotent stem cells – our iPSC facility, with the ‘i’ standing for ‘induced’ – can be really interesting for a range of companies. On a small scale, it is already being used by external parties and we are working with Sanquinnovate [Sanquin’s innovation department, ed.] to set this up more commercially. For example, we are working on making the iPSC facility GMP-compliant – a lengthy process – so that the cellular products are cleared for use with patients. But there are also the companies that test new drugs and want to use cellular models for that. They can utilise the iPSC facility too.”

“This lab-grown blood is really only meant for special cases. Blood donors will always be needed.”

Target group
Does the research into lab-grown blood mean the end of the blood donor system in the long term? “Certainly not,” says Van den Akker. “We will continue to be highly dependent on the hundreds of thousands of blood donors who give blood at Sanquin. Growing blood for transfusion in a cost-efficient way and on a scale large enough to substitute all these donors – I don’t see that happening anytime soon. We will probably be able to bring the cost down a bit at some point, but it won’t be enough to make up our standard provision for hospitals. This lab-grown blood is really only meant for special cases, for example for patients with sickle cell disease, an abnormality of the red blood cells. They need to get frequent blood transfusions. But the more often you get a blood transfusion, the higher the chance that you develop antibodies against donor blood. The reason for this is that in addition to the well-known blood groups, rhesus and  ABO, there are many more blood groups. It can then get increasingly difficult to find donor blood that is a perfect match. Wouldn’t it be great if in these cases we could use the patient’s own stem cells to grow new, healthy blood outside the body, which we could then administer without running the risk of triggering immune responses?”

A broader perspective
There are also ethical, social and legal aspects to consider in relation to lab-grown blood. For example, do patients even want to receive lab-grown blood? Sometimes people have negative associations with genetic manipulation. And what is the legal status of this blood? To approach this side of the story, the research groups within the project work with Sanquin’s Donor Studies department. This department looks into the best ways for involving the various parties – donors, patients, clinicians, policymakers and the public – with the debate around stem cells and lab-grown blood. “We’ve already held a number of public events at patients’ associations about our research into lab-grown blood,” says Van den Akker. “The reactions and questions we get from the public at events like this are really valuable for us. They give us a broader perspective on product development.”