Remote-controlled cells

02 July 2019

Interview with 

Alicia El Haj, University of Birmingham

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Stem cell

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You’ve heard of a remote-controlled car, but what about a remote-controlled stem cell? A team at the University of Birmingham have just launched a project to use magnetic nanoparticles that can be glued onto receptors on the surfaces of cells and used to control where those cells go in the body and what they do. Alicia El Haj, who is leading the initiative, presented the work at a conference in Cambridge this week. By using a magnetic field, the magnetised cells can be guided to where they’re needed and the magnetic field pulsed to make the cells transform into new cell types or secrete growth and repair factors. Chris Smith spoke to Alicia, to find out more...

Alicia - I'm interested in cell therapies; how we use cells to treat patients and cure disease and the problem we have is how to control cells. How do we actually make cells do what we want when we put them in the body, so my technology is a platform technology where we control cells.

Chris - Remote controlled cells?

Alicia - Yes that's right, because the whole aim is to be able to control them from outside of the body.

Chris - I was joking when I said that; is that what you can really do, actually dictate where cells go and what they do when they get there?

Alicia - Yes. So what we use is the principles of magnetics. We use magnetic fields to actually move cells around the body. We tag the cells with magnetic nanoparticles which are very very small and then we can actually visualise them as well using MRI technology.

Chris - Tell me about these nanoparticles then, how do you get them to stick only onto the cells you want control and what they made of?

Alicia - So we attach the cells outside of the body and we attach them to specific receptors that are located on those cell types. And they're made of iron oxide and actually we naturally have iron oxides in our body so it's something that the body doesn't reject.

Chris - Essentially then, I would have some cells taken out of me or they might even come from someone else then and you add this collection of nanoparticles to the cells in a dish and what, they glue on in the right place on the cells?

Alicia - We can use peptides, small molecules that we can attach onto the surface of the particle and that binds to the receptor on the membrane of the cell. And what's nice is the principles our based on mechanics so receptors in our body are actually mechanically activatable, which I don't think people know as much about, and so we can actually move the particle and it operates the mechanical switch on the receptor leading to a downstream response.

Chris - Once the cells been decorated with the nanoparticles, how'd you get them back in the body then, do you inject them?

Alicia - Yes. It aligns itself with is an injectable cell therapy. We inject into an organ such as the knee for cartilage repair, or into sites of bone damage for osteoporosis when we can actually localise it in an injectable format.

Chris - And how do you then dictate to the cells I want you to go to here, but not to here?

Alicia - We can use magnetic fields to target those cells to specific regions of the body, that's the principal. The particles get attracted to the magnetic fields and get localised to the sites we want them to.

Chris - Do they essentially drag the cell there then?

Alicia - Yes, basically.

Chris - And if you make those magnetic fields wobble, does that mean you can make the cells wobble and that could in turn activate the switches?

Alicia - Yes, that's the idea. We change the magnetic gradient, then the particle moves in the gradient, and it can be very small movements, and it sets up forces on the receptors in order of 6 to 8 piconewtons, and those forces are enough to activate and open the cell’s receptors.

Chris - How big’s a piconewton? Because I’m aware that one newton is, if I lift up an apple, that’s one newton, isn’t it, roughly speaking it’s a hundred grams. So how big is a piconewton then?

Alicia - Small.

Chris - That’s a get out. You’re getting out of jail free with that. Okay. We have these cells, they’ve got these particles on the surface, you can vibrate them with these magnetic fields, as a result your throwing these switches backwards and forwards. How do those switches, though, change what the cell does?

Alicia - The particles attach to the receptor, and when they move they activate the receptor and you get a downstream signal. That signal can be a variety of different signals, but what that does is lead into, effectively, a  gene activation, and then you have an expression of different proteins. So, what we want to do is actually control a cells type. If you think about it you have cartilage, bone, different cell types in your body. What we can do is take these stem cells that could be anything and by changing the receptor activation, we can then turn them into bone and turn them into cartilage. We can turn them into different types of tissue. So you can imagine we can inject in the cells, we can then remotely change the way that the cells behave, and then form tissues in the body. That’s the ultimate aim.

Chris - There’s not a chance the nanoparticles could fall off the stem cell, fall onto a heart cell and I accidentally turn my heart into a lump of bone and it doesn’t pump so well?

Alicia - No. Actually, eventually, the particles are internalised in the cell and what we’ve studied is that it changes the way that the particles are, so they are no longer able to bind to other cell types.

Chris - So there’s no danger that a person who is going on their flight and goes through a metal detector at the airport is going to accidentally activate all their stem cells downstream of this and  when they arrive at their destination they aren’t going to look like their passport photo anymore?

Alicia - People always ask me that question. Am I going to be attached to the fridge magnet? I feel that the point is that we have quite a lot of iron in our body anyway and actually the amount of iron that we are putting in is nowhere near the level of what you’d eat in a steak. The other side to it, I think, is basically that anything will be cleared from the body eventually so you won’t be permanently magnetised.

Chris - I can’t push these cells into an abnormal route of development. They’re not going to become cancerous through being stimulated in this way, for example?

Alicia - Yeah, that is something that we have to be really careful of. We have to actually check that this isn’t the case. So far in our hands we have not seen any evidence of that happening.

Chris - Is this far off? Because it sounds a bit space-age.

Alicia - It does. But actually, we’ve just received a significant amount of funding so we’re going to be developing this over the next five years. We would like to think that we can reach patients in a five year window.

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