Editorial: “US stem cell research leaves the Bush era behind“
AFTER years of hype, controversy and disappointment, stem cell treatments may finally be poised to reach masses of patients. The world’s first successful implant of a synthetic windpipe raises the prospect of implanting patients with a host of “off-the-peg” synthetic structures coated with their own stem cells. And in South Korea last week, regulators became the first in the world to approve for sale to hospitals a stem cell therapy for people who have had heart attacks.
Further from the clinic, but still with huge mass-treatment potential, are procedures to grow teeth from scratch using stem cell technology (see “Stem cell researchers show their teeth”) and to recreate a person’s blood in its entirety, following identification of the stem cell from which all types of blood cell originate.
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Amid all of this progress, the most exciting development is the successful implantation of a synthetic section of windpipe into a 36-year-old man whose own cancerous trachea had to be removed. The procedure, conducted on 9 June at the in Stockholm, Sweden, by of the Karolinska Institute, was announced only after the patient was pronounced fit enough to go home last week.
This is not the first trachea transplant operation Macchiarini has performed – in 2008 he transplanted a donated trachea. No donor was needed for the new procedure, giving it mass potential. Instead the tissue was custom-built to fit the patient, then coated inside and out with his own stem cells.
“The organ was custom-built to fit the patient exactly, then coated with his own stem cells”
The treatment began after of University College London received detailed scans of the patient’s diseased trachea. Using these, Seifalian constructed a bespoke replacement from a novel polymeric material that he has developed and patented.
Two days before the operation, the team took 200 millilitres of bone marrow from the patient and from this extracted 40 millilitres of mesenchymal stem cells. By pouring these on top of the synthetic organ in a shoebox-sized bioreactor developed by of Holliston, Massachusetts, the trachea was successfully coated inside and out with the patient’s own cells.
During surgery, Macchiarini’s final touch was to add patches of the patient’s nose lining to the inner surface of the trachea. These later grew into a layer of epithelial cells matching those lining the inner surfaces of the respiratory tract.
Seifalian says that the properties of the material can be varied to suit the application. For instance, the polymer scaffold can be designed either to last a lifetime, or to safely decay away to be replaced entirely by new tissue, opening up the possibility of treating children who would outgrow a permanent implant.
“The big conceptual breakthrough is that we can move from transplanting organs to manufacturing them,” says David Green, the president of Harvard Bioscience – although he adds that the concept would work best for simple structures such as tracheas, ureters and blood vessels.
“The big breakthrough is that we can move from transplanting organs to manufacturing them”
In another stem cell development, a company called based in Seongnam, South Korea, became the first in the world to receive official approval for a stem-cell-based procedure to treat people who have survived heart attacks. The announcement may help the country regain a reputation for pioneering stem cell research that suffered in the wake of a stem cell scandal there five years ago.
In the newly approved procedure, stem cells are extracted from the patient’s bone marrow, multiplied in the lab then injected directly into the heart through the coronary artery.
Little clinical data is publicly available to prove that the procedure benefits patients, but according to last week, the company says that in trials, patients showed 6 per cent improvements in heart function six months after the procedure, compared with untreated patients.
The level of improvement may seem small but it is “promising”, says Christopher Calhoun of in San Diego, California, which is also developing a stem cell procedure to treat heart attacks.
“But there is a cost of using bone marrow cells, as these require three to four weeks to prepare,” says Calhoun. He adds that Cytori’s treatment instead relies on stem cells that can be extracted from a biopsy of abdominal fat, purified and then re-injected within a day. The procedure is still in , but the company hopes to apply this year for approval in Europe.
The world will be watching to check if the South Korean treatment works. Unofficial stem cell treatments have been offered by private companies around the world, especially in eastern Europe and Russia, and desperate patients against paying for the unproven treatments.
A final piece of good news is the identification of the “mother” stem cell from which all types of blood cell originate, from the red blood cells that supply oxygen, to the white blood cells that provide immunity. This raises the possibility of being able to completely reconstitute a patient’s blood – perhaps after chemotherapy for leukaemia – from a single cell extracted from bone marrow before treatment began. At present, such patients receive new bone marrow from tissue-matched donors – but only a third of patients find a donor.
Researchers have known for years that these haematopoietic stem cells exist in the bone marrow. It took 20 years of complex experiments in mice, but at the University of Toronto in Ontario, Canada, has finally isolated them (Science, ).
“Our work has provided the first sighting, so to speak, of the cell we have known about for many years,” says Dick.
Stem cell researchers show their teeth
It may be time to redefine the concept of false teeth. A tooth grown from embryonic cells has been successfully transplanted into the jaw of a mouse. The transplant is a step towards providing artificial replacements for donor organs that are in short supply.
To create the tooth, at Tokyo University of Science in Japan and colleagues took cells destined to become teeth from mouse embryos. The cells were implanted into an adult mouse, beneath a membrane that surrounds the kidney.
Two months later, the cells had developed into a molar (pictured) complete with a periodontal ligament – fibres that attach the tooth to bone. The team extracted the tooth and implanted it into the jawbone of another mouse. Within 30 days, blood vessels and nerves surrounded the transplant, which functioned as if it were a native tooth ().
at Harvard School of Dental Medicine says the work is “very elegant”. She adds that researchers may be able to recreate the results using adult stem cells or cells found in wisdom teeth.
Growing teeth atop a kidney currently prevents this approach from being practical for human tooth replacement, says Paul Sharpe at King’s College London. The next big advance will come when the budding tooth cells can be cultivated outside the body, he says. Melissae Fellet
