Early test of stem cell joint repair
“Disabled people could soon re-grow damaged or diseased limb joints,” said the Daily Mirror. The newspaper said that the prospect of a new technique, using people’s own stem cells rather than transplanted ones “offers hope to millions suffering crippling pain”.
The study behind this news attempted to grow new cartilage in rabbits by drawing the rabbits’ own circulating stem cells to a scaffolding of bone-like substances implanted into their shoulder joints. To assess the technique the researchers then observed the rabbits’ movement and took samples from the joint to see if new cartilage had formed. The rabbits regenerated cartilage and were soon able to bear weight.
The real test of this technology will come if it is eventually applied to humans. While the researchers have tried growing cartilage to attach to artificial joints they say that regeneration of other tissues may also be possible with their technique. However, this type of research proceeds in small steps and so it is too soon to say if this could ever be a reliable alternative to a simple artificial hip replacement in humans.
Where did the story come from?
The study was carried out by researchers from Columbia University Medical Center, the University of Missouri and Clemson University in the US. It was funded by the New York State Stem Cell Science programme and the US National Institutes of Health. The study was published in the peer-reviewed medical journal The Lancet.
Several newspapers have accurately reported this research, with some pointing out that experts have said that even if the technique is successful in eventual human trials, a conventional hip replacement might still be the best option. The Daily Mirror goes further, claiming that this early animal research offers “new hope for millions”.
What kind of research was this?
The researchers explain that they wanted to test a new approach to generating new tissues. In this case, they wanted to test whether they could grow new sections of the cartilage naturally found on the surface of joints. Rather than directly transplanting stem cells from an external source, which some experiments have attempted, they instead wanted to provide an artificial surface that could attract the body’s own circulating stem cells and encourage them to deposit and grow on this artificial scaffolding.
The study was well conducted, and the research paper features cautious reminders that this is very preliminary work that still needs much more research to assess the feasibility of applying this technology to humans.
What did the research involve?
The researchers designed a ‘proof of concept’ study to see if it was technically possible to grow new cartilage in rabbits by attracting their circulating stem cells to a new form of scaffolding.
They compared two ‘bioscaffolds’ in an experiment on 23 rabbits. Ten scaffolds were covered in a growth factor called TGFβ3 and implanted into the rabbits, while ten rabbits were implanted with scaffolds lacking the growth factor chemical. Three rabbits also had operations to remove the joint without a bioscaffold replacement (the ‘defect only’ rabbits).
To produce these bioscaffolds, the researchers first used a computer to trace the surface shape and size of a rabbit shoulder joint. They then made a bioscaffold out of a composite of a biodegradable polymer, a polyester and a substance called hydroxyapatite, a mineral that forms a large part of normal bone.
The whole joint surface of the shoulder in the rabbits was then surgically removed and replaced with these bioscaffolds that either lacked or contained the transforming growth factor. The researchers then assessed the movement of the joints and ability of the rabbits’ shoulders to bear weight at 1–2, 3–4 and 5–8 weeks after surgery. At four months they took a sample of bone and cartilage from the live rabbits and checked them for things such as cracks, thickness, density, cell numbers and mechanical properties.
What were the basic results?
All the animals in the group given the scaffolds infused with growth factor fully resumed weight bearing and movement 3–4 weeks after surgery. The rabbits that had received the bioscaffolds infused with growth factor showed more consistent improvement than the rabbits that had received the bioscaffolds lacking the growth factor. Defect-only rabbits limped at all times.
When the sample of scaffolding and cartilage was removed at four months after surgery, joint-facing surfaces of the TGFβ3-infused bioscaffolds were fully covered with hyaline cartilage, a pad of tough but flexible cartilage that naturally lines joints. There was only isolated cartilage formation in the other implant group and no cartilage formation in the defect-only rabbits.
How did the researchers interpret the results?
The researchers say that their findings suggest that the cartilage layer across the entire surface of synovial joints (lubricated, freely moving joints) “can regenerate without cell transplantation”.
They go on to call for further investigation into the technique, saying that the regeneration of complex tissues seems probable when using ‘homing’ (having a surface or environment that attracts the body’s circulating cells) in tissues that need repair.
Conclusion
This interesting study has demonstrated the potential of a new technique. The researchers point out the areas that need further investigation:
- They do not yet know where the stem cells (or progenitor early cartilage cells) came from. Although they think that some of these cells are derived from stem or progenitor cells of synovium, bone marrow, fat cells and perhaps blood vessels, more research will be needed to find out exactly where they came from.
- They suspect that if TGFβ3 can attract multiple cell types then more research will be needed to find out how to target the specific cell populations needed for the regeneration of more complex tissues.
- They say that it is good news that the regenerated cartilage is strong enough for weight bearing in rabbits.
The real test of this technology will come if it is eventually applied to humans. The researchers were not just thinking of growing cartilage to attach to artificial joints, and explain that regeneration of other tissues may also be possible with their technique. However, this type of research proceeds in small steps and so it is too soon to say if this could ever be a reliable alternative to a simple artificial hip replacement in humans.
