Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Transplant rejection averted by simple light exposure in Stanford animal study

06.05.2004


One of the unfortunate side effects of bone marrow and stem cell transplantation is that the newly implanted cells often stage an internal attack against the patient they’re intended to help. Stanford University School of Medicine researchers now have a better grasp of this phenomenon, known as graft-versus-host disease, or GVHD, and have proposed a possible method of prevention: simple ultraviolet light.



In a new animal study, researchers identified the principal culprit in GVHD: an immune cell in the skin known as a Langerhans cell. These cells normally function as flag posts for the immune system, signaling infection-fighting T-cells to come to a particular site to fight off a virus or bacteria. But in transplants, they do patients a great disservice, alerting T-cells to attack the patient’s own tissues, researchers found.

The researchers were able to effectively eliminate the Langerhans cells in transplanted mice by exposing them to ultraviolet light, giving the animals mild sunburn. Transplanted mice that received this treatment experienced no GVHD while those that didn’t showed severe signs of the disease, said Edgar Engleman, MD, professor of pathology and medicine and senior author of the study.


"The experiment not only provided the proof that these cells cause graft-versus-host disease, but also provides a way of thinking about how you might prevent it," said Engleman, who also directs the Stanford Blood Center. The study appears in the May issue of the journal Nature Medicine.

Bone marrow or stem cell transplants are commonly used to treat patients with cancers of the blood system, such as leukemia, lymphoma or myeloma. Patients first receive radiation treatment to wipe out their defective immune systems, which then are replaced by healthy donor cells.

Sometimes, however, the process fails as GVHD sets in. The effects of the disease are most commonly seen in the skin as a reddish rash or, in more severe cases, as skin that blisters and peels.

The Stanford scientists first suspected that Langerhans cells might have a major role in GVHD after their earlier experiments showed these cells were resistant to radiation and persisted in the skin for a long time, said Miriam Merad, MD, PhD, a former postdoctoral scholar in Engelman’s lab and the first author of the study. The discovery was "shocking," Engleman said, as all other white blood cells have a short half-life and are frequently replaced. The Langerhans cells don’t change unless they’re disturbed in some way, say by inflammation, he said.

The scientists surmised that these cells might linger in the skin of a transplant patient and instigate trouble. Their latest experiments bore this out.

The researchers tested their theory in two different sets of mice. In one group, the animals had their own Langerhans cells intact. When these animals were transplanted, the Langerhans cells triggered a response and the mice developed severe GVHD. In a second group, the scientists replaced the animals’ Langerhans cells with other cells. When these mice underwent transplant, they remained protected from GVHD.

The scientists took it a step further. They exposed the vulnerable mice - those with their own Langerhans cells - to ultraviolet light using a sunlamp. The sun exposure depleted the Langerhans cells and effectively protected the mice from the disease, said Merad, who is now based at the Mount Sinai School of Medicine.

The researchers said the results present a promising option for transplant patients and could be the basis for clinical trials in which patients are exposed to ultraviolet light before treatment.

"What we would do is try to eliminate the host Langerhans cells before the transplant, as we did in the mice," Merad said. She noted that dermatologists now use ultraviolet light to treat some skin diseases, administering it to patients inside a chamber under controlled circumstances to avoid burning.

Engleman said the ultraviolet treatment would have to be carefully administered to patients before bone marrow or stem cell transplantation to avoid harmful side effects. "The trick is deplete the host Langerhans cells in a manner that doesn’t cause other unwanted effects," he said.


Other Stanford researchers in the study include Petra Hoffman, PhD; Erik Ranheim, MD, PhD; Markus G. Manz, MD; Irving Weissman, MD; and Samuel Strober, MD. Other collaborators included Sarah Slaymaker and Israel Charo, MD, PhD, of UCSF; Sergio A. Lira, MD, PhD, of Mount Sinai; and Donald N. Cook, MD, of Duke University.

The study was funded by the National Institutes of Health and by a grant from the Irene Diamond Fund.

Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children’s Hospital at Stanford. For more information, please visit the Web site of the medical center’s Office of Communication & Public Affairs at http://mednews.stanford.edu.

Ruthann Richter | EurekAlert!
Further information:
http://mednews.stanford.edu

More articles from Health and Medicine:

nachricht 'Exciting' discovery on path to develop new type of vaccine to treat global viruses
18.09.2017 | University of Southampton

nachricht A new approach to high insulin levels
18.09.2017 | Schweizerischer Nationalfonds SNF

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

Im Focus: Silencing bacteria

HZI researchers pave the way for new agents that render hospital pathogens mute

Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...

Im Focus: Artificial Enzymes for Hydrogen Conversion

Scientists from the MPI for Chemical Energy Conversion report in the first issue of the new journal JOULE.

Cell Press has just released the first issue of Joule, a new journal dedicated to sustainable energy research. In this issue James Birrell, Olaf Rüdiger,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

New quantum phenomena in graphene superlattices

19.09.2017 | Physics and Astronomy

A simple additive to improve film quality

19.09.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>