Stem Cells Regrow Long Bones – In-Depth Doctor’s Interview


John A. Szivek, PhD, Professor, Orthopaedic Surgery, William and Sylvia Rubin Chair of Orthopedic Research, Director, Robert G. Volz Orthopedic Research Laboratory and Senior Scientist at the University of Arizona Arthritis Center talks about a new stem cell technique to help form new bones.

Interview conducted by Ivanhoe Broadcast News in May 2019.

So, we met Yudith who had a piece broken out of her bone. How is your research going. How would that help somebody like her?

SZIVEK: Typically these patients that have these very long defects that are caused by car accidents or by cancer resections or any sort of really traumatic injury – typically they would get a type of surgery where the surgeon will use a piece of cadaver bone to replace the damaged bone or the piece of bone that’s missing. Often those procedures fail after a few years because the bone will bond to the ends of the cadaver bone, the dead bone, but unfortunately it never replaces that dead bone. Consequently, that dead bone fills up with cracks over time and it will break. Once that happens the patient goes back to the surgeon for another surgery. What we’re trying to do instead is to find a way to regrow the bone that was damaged, so that it’s living bone. Living bone can adapt and it can take care of any cracks that form in it. The way we’re doing that is we start off with creating what’s called a scaffold. The scaffold is just a template. That template will help that new bone form in the right shape and structure. We fill these scaffolds for the patients with their own stem cells. We call them adult stem cells and we extract those stem cells from the patient’s own fat. The advantage of doing that is there’s no rejection potential because we’re using the person’s own cells. The other advantage is that if we can fill our scaffold with these cells, the bone will start to form throughout the length of that scaffold. It’ll form more quickly and give the patient a chance to get up and walk around on it so that their bone will adapt to the right structure for them. So, it’s kind of a form of personalized medicine for these patients.

How are the weak parts of the scaffold protected? What happens to keep those from bending?

SZIVEK: We were discussing the attachment sites at the bone ends where the normal bone that the patient still has will attach to the scaffold and will allow bone to grow over. Initially while we’re holding this in place so that the bone will grow over it, we use a rod. You can’t see the rod in this case, but you can see two screws. Those two screws hold that rod in place. It goes through the marrow section and it holds the scaffold in place and that protects this area from breaking until new bone has formed over it and attaches securely to the two ends.

And then you pull the rod out?

SZIVEK: We do. These rods are often used in simple fractures as well – a fracture where there’s just a clean break. So these rods are often used in patients where there’s a simple fracture – a fracture that just goes through the bone. The rods are primarily used because they are easy to put in and to take out. The surgeon can place these either from one end of the bone or from the other end of the bone, and then they use the two screws I talked about earlier as locking screws. Those prevent anything from twisting. Those screws can be taken out pretty easily, and they’re usually taken out relatively early. Once they’re out, the surgeon can also remove the rod, and once that’s done, then this area has to protect itself. But while the rods in there it protects this middle section of the bone while there’s new bone forming.

So the scaffold, where does that come from?

SZIVEK: The way that we manufacture these scaffolds is that we scan the bone. We can scan the bone of the patient in a C.T. scanner and once we’ve got that image, we send it to a computer. We can send that image data to a 3D printer and the 3D printer will print something that looks like this. And again, that 3D-printed image is very similar to the bone of the patient, so that when we put it into the patient, that patient will end up with a structure that’s similar to their own bone.

How many stem cells would you put in?

SZIVEK: Well at the moment we’re using something in the neighborhood of about 2 million cells. We’ve found that that number of cells seems to work pretty well. If you use more cells, it’s probably more advantageous but we try to limit the length of time that the cells are out of the patient. Consequently, we can in a short period of time generate that number of cells out of a small amount of fat that we extract from the patient.

So two million stem cells – is that a handful? Is that a fingerful? What does that look like?

SZIVEK: That’s a pretty small amount. Usually the amount of fat that we extract is about 10 to 15 grams of fat. And that will generate over 2 million cells.

What is the timeframe between setting up the scaffold, putting in the rod, taking the rod out and somebody being able to walk away?

SZIVEK: At the moment the timeframes that we’re looking at are placing the rod in, removing the screws after something in the neighborhood of three to six months, and removing the rod in about six to nine months. So, it’s a reasonable timeframe. It’s the sort of timeframe that we tend to use even when there’s a simple fracture. These rods are rarely taken out before three months but they’re often taken out of the patient by the time nine months rolls around.

This research is funded with a DOD grant. Why is that? Where did that come from?

SZIVEK: I think the reason that the Department of Defense is so interested in this work is that many soldiers are very badly injured on the battlefield. Typically, those injuries are so difficult to treat using any treatment that’s currently available, that the DOD has often decided that amputation is the better solution. We don’t think that amputation is a very good solution. We believe that using our approach could regrow the bones for these soldiers and they would then be able to return to active military service.

What kind of timeframe are you in for human trials?

SZIVEK: That’s a very difficult question to ask but we have had some very good success recently. If that success is acceptable to the FDA, then we could go to a clinical trial – a phase one clinical trial fairly quickly, it depends on how the FDA views our results.

Results are from animal trials or from test tube trials?

SZIVEK: The results are from animal trials.

And sheep, you said, is what you’re using?

SZIVEK: We’re using a sheep model, yes.

So the phase one would be just here at UA?

SZIVEK: Yes. The phase one trial would be at Banner Hospital which is affiliated with the university. And it would be a limited number of patients in order to make sure that the technology that we see as being so successful in our sheep model is actually very successful in a patient as well.

And phase one – five patients, 10?

SZIVEK: I think it would be a small number. It would be less than 10 patients, yes.

What haven’t I asked you that we should include in the story?

SZIVEK: Well, we haven’t talked about the sensors if you had an interest in that.

Let’s talk about the sensors and how they work.

SZIVEK: One of the reasons that we had an interest in taking measurements while we were doing this experiment is that it’s pretty apparent that exercise affects the rate at which your bones turn over and potentially the rate at which they grow. And the only way that we’ve found that we can take these measurements is to attach sensors to our scaffolds, so that’s what we’ve been doing. We’ve been taking these sensors and attaching them directly to the scaffolds. And we’re now working on some implantable radio devices that would be about the size of the sensors so that we could actually put these into patients, have the patients exercise, and we could monitor their exercise, monitor their rehabilitation and be able to figure out how to most quickly get bone to form.

So, then what you’re measuring is bone growth?

SZIVEK: What we’re measuring with the sensors is how much load is passing through that bone. So, you can imagine that some of the patients will be more active than others. And we’re hoping that those active patients form bone more quickly. If they exercise daily, we’ll be able to monitor the exercise. And as my surgeon friends tell me they won’t have to rely on the patient’s reporting that because we’ll be able to detect that from the sensors. So even if the patients forget or they’re not telling us exactly the types of exercises they’re doing, we will be able to measure that with our sensor.

Will the sensor will download into the computer or something like that?

SZIVEK: The sensor will download into a cell phone which is really nice because once we have that system working, the cell phone will actually be able to instruct the patient as well. So if they are overloading their leg, the cell phone which can talk, will tell them you’re jumping too hard. You are running too fast. And that’s the advantage of having the ability to take the measurement and send it to a cell phone. And nowadays many people have smartphones.

So, this is part of the research as well?



This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.

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