Nav: Home

Troublesome T cells have a healing side

April 14, 2016

Immune system cells linked to allergies also turn out to direct healing of mouse muscle wounds when paired with biologic "scaffolding" to support them, researchers from Johns Hopkins and the Kennedy Krieger Institute report. The finding, described in the April 15 issue of Science, adds to evidence that the immune system is key not just to fighting infectious and other diseases but also to kick-starting healing after an injury. They also indicate that so-called biomaterial scaffolds can more effectively spur healing if designed to "partner" with immune cells, the researchers say.

"In previous research, we've seen different immune system responses to the same biomaterial implanted in different tissues or environments, and that got us interested in how biomaterials might stimulate the immune system to promote regeneration," says Jennifer Elisseeff, Ph.D., professor of ophthalmology and biomedical engineering at the Johns Hopkins University School of Medicine. "We still have a lot to learn, but this study is a step toward designing materials to elicit a beneficial immune response."

Elisseeff's research group designs biodegradable scaffolds, made of materials such as collagen, that have shown promise in promoting regrowth of damaged tissue, in part by giving the body's own stem cells a place to anchor and begin their work. But in the past few years, she says, other research groups have found evidence that such scaffolds could also spark healing activity from immune cells.

To learn more about the immune cells involved and their response, then-graduate student Kaitlyn Sadtler, Ph.D., worked with other researchers in Elisseeff's lab and specialists in cancer immunology. They surgically removed part of the thigh muscles of mice and implanted scaffolds known to promote healing in animals. After a week, wound sites with scaffolds had more white blood cells than did wounds without scaffolds, and many of those cells were churning out a chemical signal, interleukin-4, that is frequently produced by so-called type 2 helper T cells.

To see what the role of those cells might be, the team did the same procedure on mice genetically modified to lack T cells and found that their wounds didn't ramp up interleukin production or heal as well as those of the normal mice. Further investigation revealed that one role of the type 2 helper T cells was to activate and train another type of immune cell, called macrophages, at the wound site. "The T cells tell the macrophages how to behave, making them pro-regenerative macrophages," says Sadtler.

Previous studies suggest several key healing roles for the macrophages: cleaning up dead or damaged cells and other debris, recruiting and supporting adult stem cells that regrow tissue, and sparking the construction of new blood vessels to fuel new tissue in the area. But the pivotal role of type 2 helper T cells in scaffolds comes as a surprise, Elisseeff says: Those cells help fend off intestinal worms, but in the developed world, they're most often associated with triggering "bad" immune responses, such as allergies. "It's interesting to see something useful coming out of this pathway," she says.

Elisseeff notes that there is still much to learn about how immune cells respond to various kinds of biomaterials that might be used as scaffolds -- an area her team continues to investigate.

"This study, in demonstrating for the first time the central role of T cells in mediating the tissue regenerative process, is truly groundbreaking," says Drew Pardoll, M.D., Ph.D., the Martin D. Abeloff Professor of Oncology in the Johns Hopkins' Kimmel Cancer Center and director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy, who collaborated with Elisseeff on the study. "I predict it will be viewed as an inflection point, where regenerative immunology goes from an idea into a field of serious study. And it opens the door for totally novel strategies to significantly enhance tissue regeneration."
-end-
Other authors on the paper are Kenneth Estrellas, Brian W. Allen, Matthew T. Wolf, Hongni Fan, Ada J. Tam, Chirag Patel, Brandon S. Luber, Hao Wang, Jonathan D. Powell and Franck Housseau of the Johns Hopkins University School of Medicine, and Kathryn R. Wagner of the Kennedy Krieger Institute.

Sadtler, Housseau, Pardoll and Elisseeff are inventors on provisional patent application No. 48317-502P01US, filed by The Johns Hopkins University related to regenerative immunology. Elisseeff holds equity in Aegeria Soft Tissue, a company that has licensed Johns Hopkins University intellectual property not directly related to the materials used in this study but similar enough that it may benefit from the results. The conflict is being managed by the Johns Hopkins Office of Policy Coordination. This work was funded by the Maryland Stem Cell Research Fund (grant number 113345), the Armed Forces Institute for Regenerative Medicine, the U.S. Department of Defense (grant number W81XWH-11-2-0022), a postdoctoral fellowship from the Hartwell Foundation, the National Cancer Institute (grant number P30CA006973), and the National Institute of Allergy and Infectious Diseases (grant number R01AI077610).

Johns Hopkins Medicine

Related Stem Cells Articles:

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.
Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.
The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.
Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.
New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.
NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.
Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.
In mice, stem cells seem to work in fighting obesity! What about stem cells in humans?
This release aims to summarize the available literature in regard to the effect of Mesenchymal Stem Cells transplantation on obesity and related comorbidities from the animal model.
TSRI researchers identify gene responsible for mesenchymal stem cells' stem-ness'
Researchers at The Scripps Research Institute recently published a study in the journal Cell Death and Differentiation identifying factors crucial to mesenchymal stem cell differentiation, providing insight into how these cells should be studied for clinical purposes.
Stem cells in intestinal lining may shed light on behavior of cancer cells
The lining of the intestines -- the epithelium -- does more than absorb nutrients from your lunch.
More Stem Cells News and Stem Cells Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Accessing Better Health
Essential health care is a right, not a privilege ... or is it? This hour, TED speakers explore how we can give everyone access to a healthier way of life, despite who you are or where you live. Guests include physician Raj Panjabi, former NYC health commissioner Mary Bassett, researcher Michael Hendryx, and neuroscientist Rachel Wurzman.
Now Playing: Science for the People

#544 Prosperity Without Growth
The societies we live in are organised around growth, objects, and driving forward a constantly expanding economy as benchmarks of success and prosperity. But this growing consumption at all costs is at odds with our understanding of what our planet can support. How do we lower the environmental impact of economic activity? How do we redefine success and prosperity separate from GDP, which politicians and governments have focused on for decades? We speak with ecological economist Tim Jackson, Professor of Sustainable Development at the University of Surrey, Director of the Centre for the Understanding of Sustainable Propserity, and author of...
Now Playing: Radiolab

An Announcement from Radiolab