Spray-on stem cells for synthetic tissue?

26 January 2009

Stem cells can survive a cell-spraying technique with promise for tissue engineering, offering a potential route to unspecialised tissue for medical applications. UK scientists Suwan Jayasinghe and co-workers at University College London have shown how mouse embryonic stem cells can be handled and precisely deposited without affecting their molecular structure. “The technique allows researchers to build biological microenvironments such as synthetic tissue at a higher resolution than other approaches” Jayasinghe’s team achieved this using bio-electrosprays, which jet a cell suspension from a conducting needle to a grounded electrode upon application of an electric field. The technique allows researchers to build biological microenvironments such as synthetic tissue at a higher resolution than other approaches. Embryonic stem cells encapsulated in a biopolymer Jayasinghe’s results imply that embryonic stem cells retain their function after bioelectrospraying Although bio-electrosprays have been used with other types of cells, this is the first time they have been used with embryonic stem cells. David Harris, an expert in stem cell research and gene therapy, based at the University of Arizona, Tucson, US, suggests that the approach has ‘tremendous potential for tissue engineering and regenerative medicine.’ As the researchers found, the bio-electrospray process does not change the stem cells at a genetic level. Their results imply that the cells remain pluripotent, meaning that they have the potential to develop into a variety of cell types. “The approach has tremendous potential for tissue engineering and regenerative medicine” – David Harris ‘The beauty of this technique as a therapeutic device,’ says Jayasinghe, ‘is that you could genetically alter the stem cells using gene therapy techniques and then build the tissue.’ As well as being used for repair and replacement, the tissue could provide a therapeutic effect, he adds. Elizabeth Davies

Bortezomib Shows Promise as Antirejection Therapy

www.medpagetoday.com/Surgery/Transplantation/12281

CINCINNATI, Dec. 29 — Kidney transplant recipients experiencing refractory acute rejection saw a quick and durable resolution after a short course of bortezomib (Velcade), investigators here said.
Action Points  <!— –>

  • Explain to patients that a drug used to treat a type of blood-related cancer showed potential as a means to treat or prevent rejection after kidney transplantation.
  • Note that the study involved only six patients.
  • Note also that bortezomib is not approved for use as antirejection therapy.

The treatment effectively quelled eight episodes of antibody-mediated rejection and concomitant acute cellular rejection in six patients, E. Steve Woodle, M.D., of the University of Cincinnati, and colleagues reported in the Dec. 27 issue of Transplantation.The drug achieved marked and prolonged reductions in donor-specific antihuman leukocyte antigen antibody levels and improved allograft function.

“Bortezomib represents the first effective antihumoral therapy with activity in humans that targets plasma cells,” the authors concluded.

A lack of direct activity against the mature plasma cell — the major antibody-producing cell — limits the effectiveness of current antihumoral therapies, including plasmapheresis, intravenous immune globulin, and polyclonal antilymphocyte antibodies.

The proteosome inhibitor bortezomib has pleiotropoic immune modulating effects, including preclinical activity against nontransformed plasma cells.

That activity, combined with dissatisfaction with standard therapies for antibody-mediated rejection, led the authors to evaluate bortezomib as treatment or prophylaxis for cell-mediated allograft rejection.

The six patients included in the study had episodes of acute rejection as defined by at least a 20% increase from baseline in serum creatinine plus histologic evidence of acute rejection by Banff criteria.

Baseline serum creatinine was defined as the mean of five consecutive measurements that immediately preceded acute rejection.

Initial rejection episodes occurred from 25 to 2,774 days after transplantation. In all cases, bortezomib was initiated after failure of a trial of one or more standard antirejection therapies.

Two patients had a second rejection episode. In one case, the initial episode occurred on posttransplant day 223 and the second on day 452. In the second case, the initial rejection episode occurred on posttransplant day 25 and the second on day 245. Recurrent episodes were treated immediately with bortezomib.

Each rejection episode was treated with a single course of bortezomib at labeled dosing.

In all cases, the immunodominant donor-specific antihuman antibody declined by more than 50% within 14 days of treatment and remained suppressed for as long as 14 months.

Every patient had one or more additional donor-specific antihuman antibodies, which declined with treatment to undetectable levels.

Principal bortezomib-related toxicities were gastrointestinal effects, thrombocytopenia, and paresthesias, all of which were transient.

The observation of recurrent rejection episodes in two patients “argues for more aggressive therapeutic approaches,” the authors said. “One such approach was used with bortezomib therapy in the third patient in this report, where bortezomib therapy was used concomitantly with additional agents.”

Additionally, antihuman antibody levels rebounded in some patients. The observation requires longer follow-up to determine the clinical significance, the authors said.

However, they noted, clinical experience with bortezomib in multiple myeloma has suggested that administration of multiple cycles of therapy might be a reasonable approach to enhance the drug’s activity.

The authors reported no potential conflicts of interest.

Organ donation in Germany

Health | 21.12.2008

“A New Chance At Life”: A Look at Organ Donation in Germany

Organ failure often means death, especially when there is a shortage of organ donors. In Germany, over 4,000 transplants occur each year, but there are still too few organ donors when compared to those in need.

To help even the balance — and increase the chances of survival for many — the European Commission recently set forth two new proposals for making organ donations and transplants easier.

One of the most important aspects laid out in these proposals is the introduction of transplantation coordinators for all large hospitals. It’s a move that’s been quite successful in several EU countries, including Spain. And it’s one that Germany will soon make, too.

“There are far too few organ donors in Germany,” said Wolfgang Arns, Head of the Transplantation Station at Cologne’s Merheim Hospital.

“Patients sometimes have to wait five, six, seven years and while they wait, they become sicker and sicker. Unfortunately that means watching as a patient’s health slips away, making them no longer ideal recipients of a transplant. They simply die while they wait.”

Like winning the lottery

In Germany, three people die every day while waiting on the transplant list. With only 4,000 organs donated each year, making it off the waiting list can seem like winning the lottery.

Two surgeons completing a transplant operationBildunterschrift: Großansicht des Bildes mit der Bildunterschrift: A donor shortage can make transplant recipients feel like lottery winners

“When the call comes, you’re just beside yourself,” said Hermann Meters, a recent recipient of a new kidney. “You’re so happy at that moment, you become absolutely scatterbrained. ”

Benjamin Hoffmann, who got a second chance at life recently when he received a new kidney, agreed. For seven-and-a-half years, the 27-year-old had to endure dialysis while waiting for an organ donor to come along.

“Three times a week, for five hours at a time, I’d be stuck with a needle and have to wait as my blood was filtered,” said Hoffmann.

Kidneys, which cleanse the body of impurities while also making sure that the body has enough salt and fluid, are the most frequently transplanted organs in Germany.

Though Hoffmann is quite happy to have finally made if off the waiting list, he prefers not think about where his new organ came from.

“It’s better not to think that it may have come from someone who died,” he said. “It’s better to simply enjoy it, this beginning of a new life.”

A gloved hand holding a human heart while preparing it for transplantBildunterschrift: Großansicht des Bildes mit der Bildunterschrift: Some recipients feel guilty about having taken another’s heart

Though one person who is listed as an organ donor can save up to seven lives when he or she dies, kidney donations can likewise come from living donors. For now, Hoffmann only knows that his organ donor was about 50 years old.

Ensuring neutrality

Eurotransplant, an organization based in Leiden, The Netherlands, arranged the transplant with Hoffmann’s physician, Arns. They won’t reveal more details, as some recipients have problems coming to terms with the idea that they are living with an organ donated by someone who may be dead.

“Working with a distribution center like Eurotransplant ensures that decisions remain neutral,” said Arns. “They have a compulsory schedule that they use to seek out potential recipients.”

Following set criteria — blood type, urgency of need, the patient’s time spent on the waiting list, among other things — the center chooses who will receive the next transplant. The organ is then shipped to one of the seven European countries which subscribe to the center’s services and is delivered to the appropriate hospital.

The bad news: side effects

Once selected, the patients have to undergo a physical to ensure they’re healthy enough to handle the new transplant. And afterwards, they need to maintain a strict medication regiment for the rest of their lives.

“These medications, of course, have side effects,” said Arns. “One of which is infection. Another is that it can cause damage in other organs. And the third is, of course, the problem that after taking the medication for a while, the body’s natural ‘health police’ get triggered and often this creates tumors after a transplant.”

The “health police” is the body’s natural immune system. But as artificial kidneys aren’t yet available, these side effects are chances that patients have to be willing to take.

And Arns, who has done transplants for over thirty years, is happy about his success.

“It’s quite a wonderful feeling,” he said. “It’s a real sense of pleasure – most of all when a former patient comes back and you just see how good they feel. It’s written all over their face.”

Jana Pareigis (cat)

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