Monoclonal antibodies preserve stem cells in mouse brains, bring promise for future studies

Using antibodies instead of traditional drugs, stem cells last significantly longer when used in pre-clinical animal models.

5:00 AM

Author | Noah Fromson

brain stem blue green slice
Human neural stem cell transplants (green) survive and migrate throughout the mouse brain (blue) when given a novel monoclonal antibody treatment. Michigan Medicine

A new approach to stem cell therapy that uses antibodies instead of traditional immunosuppressant drugs robustly preserves cells in mouse brains and has potential to fast-track trials in humans, a Michigan Medicine study suggests.

For this study, researchers used monoclonal antibodies to suppress the immune system in mice and compared the results to traditional immunosuppression with the medications tacrolimus and mycophenolate mofetil. They tracked implanted human neural stem cell survival using luciferase, the protein that makes fireflies glow.

Results published in Clinical and Translational Medicine reveal that suppression with monoclonal antibodies enabled long-term survival of human stem cell transplants in mouse brains for at least six to eight months, while the cell grafts did not survive more than two weeks in most animals when using standard immunosuppressant drugs.

SEE ALSO: An easier way to grow model organs (uofmhealth.org)

"This study makes it clear that using monoclonal antibodies is better for the study of stem cell transplants in the brain and spinal cord over the long term," said lead author Kevin Chen, M.D., a neurosurgeon at University of Michigan Health and clinical assistant professor of neurosurgery at U-M Medical School. "The cells survived for so long with fewer injections and less toxicity from immunosuppression when using monoclonal antibodies. This will enable more experiments and studies of stem cell therapies, bringing more promise for their future in the neurosciences."

Researchers sought to combat a longstanding obstacle for stem cell therapy in neurological disease of keeping cells alive when testing them in pre-clinical animal models. Many scientists have relied on immunosuppressant medications to keep the animals' immune systems from rejecting stem cells, Chen says, but they eventually fail and torpedo the process.

"In many of these experiments, we would only see around a third of animals have cells survive and have no way to interpret the results," he said. "It gets expensive in stem cell therapy to conduct these experiments and not have the cells survive."

Like Podcasts? Add the Michigan Medicine News Break on Spotify, Apple Podcasts or anywhere you listen to podcasts.

Traditional immunosuppressant drugs are less selective than monoclonal antibodies, which, in this study, targeted two immune proteins. The antibodies have only been analyzed in a handful of stem cell therapy studies for the nervous system. However, this study tracked cell survival for as long as eight months – one of the longest time points published for stem cells in the brain and spinal cord.

This study lays the groundwork for understanding how transplanted stem cells integrate into the brain, says senior author Eva Feldman, M.D., Ph.D., James W. Albers Distinguished Professor at U-M, the Russell N. DeJong Professor of Neurology and director of the NeuroNetwork for Emerging Therapies at Michigan Medicine. "Our new findings continue to support advancing stem cell therapies into human clinical trials," Feldman said. "Stem cell therapy remains a beacon of hope for neurological diseases."

SEE ALSO: Mathematical model could bring us closer to effective stem cell therapies (uofmhealth.org)

Live your healthiest life: Get tips from top experts weekly. Subscribe to the Michigan Health blog newsletter

Headlines from the frontlines: The power of scientific discovery harnessed and delivered to your inbox every week. Subscribe to the Michigan Health Lab blog newsletterAdditional authors include Lisa M. McGinley, Ph.D., Shayna N. Mason, B.S., DianaM. Rigan, B.S., Jacquelin F. Kwentus, B.S., John M. Hayes, B.A., Emily D. Glass, B.S., Evan L. Reynolds, Ph.D., Geoffrey G. Murphy, Ph.D., all of University of Michigan

This study was supported by the National Institute on Aging, The Handleman Emerging Scholar Program, The Robert E. Nederlander Sr. Program for Alzheimer's Research, The Sinai Medical Staff Foundation, and and The NeuroNetwork for Emerging Therapies

Paper cited: "Monoclonal antibody-mediated immunosuppression enables long-term survival of transplanted human neural stem cells in mouse brain," Clinical and Translational Medicine. DOI: 10.1002/ctm2.1046


More Articles About: Lab Report Neurosurgery & Neurological Procedures Neurological (Brain) Conditions Basic Science and Laboratory Research All Research Topics
Health Lab word mark overlaying blue cells
Health Lab

Explore a variety of healthcare news & stories by visiting the Health Lab home page for more articles.

Media Contact Public Relations

Department of Communication at Michigan Medicine

[email protected]

734-764-2220

Stay Informed

Want top health & research news weekly? Sign up for Health Lab’s newsletters today!

Subscribe
Featured News & Stories Florescent image of a human ovarian follicle
Health Lab
Spatial atlas of the human ovary with cell-level resolution will bolster reproductive research
New map of the ovary provides a deeper understanding of how oocytes interact with the surrounding cells during the normal maturation process, and how the function of the follicles may break down in aging or fertility related diseases.
A CT scan of healthy lungs
Health Lab
Study reveals potential to reverse lung fibrosis using the body’s own healing technique
A recent U-M study uncovers a pathway utilized during normal wound healing that has the potential to reverse idiopathic pulmonary fibrosis.
Photo of a cluttered, messy garage
Health Lab
Chemicals stored in home garages linked to ALS risk
A Michigan Medicine study finds that storing chemicals in a garage at home may associate with an increased risk of ALS.
Close up image of red blood cells moving through veins
Health Lab
Discovery reveals how this common stinky gas is processed to promote blood vessel growth
A new collaborative study, examined the interaction between three naturally occurring gases — nitric oxide (NO), oxygen, and H2S — during generation of new blood vessels, called angiogenesis.
Photo of two silhouettes in a hallway
Health Lab
Most new doctors face some form of sexual harassment, even after #MeToo
Sexual harassment of all kinds is a common experience among first-year medical residents, also known as interns, especially those in surgical specialties, but it may be declining.
Health Lab
Father’s cancerous brain tumor found weeks after the birth of his daughter
Father’s cancerous brain tumor found weeks after the birth of his daughter