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Osteogenic stem cells: treating bone disease at its origin
Researchers are hopeful that the cells will one day be part of the regular regimen of osteoporosis treatments.
OXFORD, England — The potential in using osteogenic stem cells for skeletal healing is significant, although there is still much to learn in how these cells can modulate and reconstruct tissue in cartilage, bone, tendon and ligament healing, according to a researcher here.
The characterization and acquisition of different stem cells, in particular, is a sensitive topic among investigators, said James T. Triffitt, clinical investigator at the Botnar Research Centre, Nuffield Orthopaedic Centre, University of Oxford. In embryos, stem cells are collected from the inner cell mass, a situation that poses ethical questions. Instead, most scientists opt to collect adult stem cells, which are present in the fetus and remain in the adult in nearly every tissue.
Despite rapid advances in the knowledge of skeletal biology, “Certain aspects concerning the origins and characteristics of the precursor cells and the sequential biological controls for their development are lacking,” he said. Still, methods are now available to amplify the appropriate cells in vitro to aid skeletal healing. Tissues that were not considered regenerative like the spinal cord, brain and the heart all contain stem cells and appear to be capable of functional tissue restoration to some extent, Triffitt said.
Early indications
Initially, the theory that stem cells have a great self-renewal potential and capacity to develop into any cell, characteristic of that cell’s lineage, was applied more to the other stem cells than to bone stem cells. But in studies involving bone marrow cells, scientists took 1/1000 of the total pelvic marrow of a young rabbit and cultured it in vitro and developed stem cells. When the researchers took 1/16,000 of these cells and put them into a culture where bone could be generated, 2 mg of bone evolved. Theoretically, if the researchers had taken the entire portion of that cell population, they would have developed 32 grams of bone.
“But this was only from 1/1000 of the pelvic marrow of a young rabbit. Therefore, from this calculation, you can see that you could potentially generate 32 kg of bone from the entire bone marrow of a young rabbit, which is twice the skeletal mass [of a grown man],” he said. “It’s an amazing amount of bone that can be generated from only a small amount of [stem] cells. It indicates the stem cell characteristics of these [marrow] cells.
“The potential is there to grow bone, but how do we get to that potential?” he said.
Forming colonies
In a study of 99 patients, Triffitt and his colleagues compared the colony-forming units in people with osteoporosis or osteoarthritis (OA), as well as a control group of normal individuals. The investigators found that there was no correlation between the number of these colony-forming units and patient age or the presence of osteoporosis or OA.
“What we did see is a difference of colony size with age. In patients with osteoporosis, we saw a lower proportion of alkaline phosphatase, the bone marker enzyme, but not in the patients with osteoarthritis,” he said.
Triffitt believes the mesenchymal stem cell differentiation pathway, which gives rise to all of these different tissues — cartilage, bone, smooth muscle, fat, tendon and ligament, and the specialized cells — changes in older patients and those with osteoporosis. “If we can manipulate this, we may be able to perhaps correct the bone-forming ability in these conditions.”
Unfortunately, there is still too little information about the basic phenomena that occur when cells are injected in vivo in physiological situations. “We’ve even looked into the genetic marking of cell populations from rabbits and humans and other animals with retroviruses, and these give a permanent integration of genes into the host chromosome. This is permanent and inheritable, and it has little effect on cell development, at least in the systems we’ve used,” he said.
For the future of stem cell therapy, stem cells can be taken from
the marrow, cultured in vitro, amplified and then either directly implanted at
the required site (autologous), injected near the damaged site or systemically
injected into the general bloodstream.
Scientists can also take cells from other tissue deposits that
may give rise to osteoblast stem cells, such as subcutaneous fat or muscle.
They can also manipulate them with bone-inducing proteins, generate the
production of stem cells and inject them into the problem areas where bone has
been compromised, or into genetic deficiencies such as those associated with
osteoporosis.
“The effective use of these cells is still a long way off;
there is still a lot of basic work to be done. But it’s amazing that some
people are trying it in humans now,” he said.
For the future of stem cell therapy, stem cells can be taken from the marrow, cultured in vitro, amplified and then either directly implanted at the required site (autologous), injected near the damaged site or systemically injected into the general bloodstream.
Scientists can also take cells from other tissue deposits that may give rise to osteoblast stem cells, such as subcutaneous fat or muscle. They can also manipulate them with bone-inducing proteins, generate the production of stem cells and inject them into the problem areas where bone has been compromised, or into genetic deficiencies such as those associated with osteoporosis.
“The effective use of these cells is still a long way off; there is still a lot of basic work to be done. But it’s amazing that some people are trying it in humans now,” he said.