World's first: Drug guides stem cells to desired location, improving their ability to heal

November 24, 2020

Scientists at Sanford Burnham Prebys Medical Discovery Institute have created a drug that can lure stem cells to damaged tissue and improve treatment efficacy--a scientific first and major advance for the field of regenerative medicine. The discovery, published in the Proceedings of the National Academy of Sciences (PNAS), could improve current stem cell therapies designed to treat such neurological disorders as spinal cord injury, stroke, amyotrophic lateral sclerosis?(ALS) and other neurodegenerative disorders; and expand their use to new conditions, such as heart disease or arthritis.

Toxic cells (green) disappeared when mice with a neurodegenerative condition received both therapeutic stem cells (red) and the drug SDV1a-which corresponded with longer lives and delayed symptom onset. These results suggest that SDV1a can be used to improve the efficacy of stem cell treatments.

"The ability to instruct a stem cell where to go in the body or to a particular region of a given organ is the Holy Grail for regenerative medicine," says Evan Y. Snyder, M.D. Ph.D., professor and director of the Center for Stem Cells & Regenerative Medicine at Sanford Burnham Prebys and senior author of the study. "Now, for the first time ever, we can direct a stem cell to a desired location and focus its therapeutic impact."

Nearly 15 years ago, Snyder and his team discovered that stem cells are drawn to inflammation--a biological "fire alarm" that signals damage has occurred. However, using inflammation as a therapeutic lure isn't feasible because an inflammatory environment can be harmful to the body. Thus, scientists have been on the hunt for tools to help stem cells migrate--or "home"--to desired places in the body. This tool would be helpful for disorders in which initial inflammatory signals fade over time--such as chronic spinal cord injury or stroke--and conditions where the role of inflammation is not clearly understood, such as heart disease.

"Thanks to decades of investment in stem cell science, we are making tremendous progress in our understanding of how these cells work and how they can be harnessed to help reverse injury or disease," says Maria T. Millan, M.D., president and CEO of the California Institute for Regenerative Medicine (CIRM), which partially funded the research. "Dr. Snyder's group has identified a drug that could boost the ability of neural stem cells to home to sites of injury and initiate repair. This candidate could help speed the development of stem cell treatments for conditions such as spinal cord injury and Alzheimer's disease."

A drug with only the "good bits"

In the study, the scientists modified CXCL12--an inflammatory molecule which Snyder's team previously discovered could guide healing stem cells to sites in need of repair--to create a drug called SDV1a. The new drug works by enhancing stem cell binding and minimizing inflammatory signaling--and can be injected anywhere to lure stem cells to a specific location without causing inflammation.

"Since inflammation can be dangerous, we modified CXCL12 by stripping away the risky bit and maximizing the good bit," says Snyder. "Now we have a drug that draws stem cells to a region of pathology, but without creating or worsening unwanted inflammation."

To demonstrate that the new drug is able to improve the efficacy of a stem cell treatment, the researchers implanted SDV1a and human neural stem cells into the brains of mice with a neurodegenerative disease called Sandhoff disease. This experiment showed SDV1a helped the human neural stem cells migrate and perform healing functions, which included extending lifespan, delaying symptom onset, and preserving motor function for much longer than the mice that didn't receive the drug. Importantly, inflammation was not activated, and the stem cells were able to suppress any pre-existing inflammation.

Next steps

The researchers have already begun testing SDV1a's ability to improve stem cell therapy in a mouse model of ALS, also known as Lou Gehrig's disease, which is caused by progressive loss of motor neurons in the brain. Previous studies conducted by Snyder's team indicated that broadening the spread of neural stem cells helps more motor neurons survive--so the scientists are hopeful that strategic placement of SDV1a will expand the terrain covered by neuroprotective stem cells and help slow the onset and progressive of the disease.

"We are optimistic that this drug's mechanism of action may potentially benefit a variety of neurodegenerative disorders, as well as non-neurological conditions such as heart disease, arthritis and even brain cancer," says Snyder. "Interestingly, because CXCL12 and its receptor are implicated in the cytokine storm that characterizes severe COVID-19, some of our insights into how to selectively inhibit inflammation without suppressing other normal processes may be useful in that arena as well."
-end-
A team effort

The co-first authors of the study are Jean-Pyo Lee of Sanford Burnham Prebys and Tulane University School of Medicine, Rodolfo Gonzalez and Runquan Zhang of Sanford Burnham Prebys. Additional study authors include Mao-Cai Yan, Srinivas Duggineni, Dustin R. Wakeman, Walter L. Niles and Yongmei Feng of Sanford Burnham Prebys; Justin Chen and Milton H. Hamblin of Tulane University School of Medicine; Edward B. Han, Xiao Fang, Yinsong Zhu and Yan Xu of Tsinghua University, Juan Wang of Tsinghua University, David A. Wenger of Jefferson Medical College; Thomas N. Seyfried of Boston College; Jing An of University of California San Diego; Richard L. Sidman of Harvard Medical School; and Ziwei Huang of Sanford Burnham Prebys and University of California San Diego.

This work was supported by the National Institutes of Health (R01-GM057761), CIRM (RS1-00225-1), the Department of Defense (W81XWH-16-1-0087-02), the National Tay-Sachs & Allied Disease Foundation, and the Children's Neurobiological Solutions Foundation. The study's DOI is 10.1073/pnas.1911444117.

About Sanford Burnham Prebys Medical Discovery Institute

Sanford Burnham Prebys is a preeminent, independent biomedical research institute dedicated to understanding human biology and disease and advancing scientific discoveries to profoundly impact human health. For more than 40 years, our research has produced breakthroughs in cancer, neuroscience, immunology and children's diseases, and is anchored by our NCI-designated Cancer Center and advanced drug discovery capabilities. For more information, visit us at SBPdiscovery.org or on Facebook at facebook.com/SBPdiscovery and on Twitter @SBPdiscovery.

Sanford Burnham Prebys Medical Discovery Institute

Related Stem Cells Articles from Brightsurf:

SUTD researchers create heart cells from stem cells using 3D printing
SUTD researchers 3D printed a micro-scaled physical device to demonstrate a new level of control in the directed differentiation of stem cells, enhancing the production of cardiomyocytes.

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

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.

Read More: Stem Cells News and Stem Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.