Transplanted neural stem cells treat ALS in mouse model

December 19, 2012

LA JOLLA, Calif., December 19, 2012 - Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is untreatable and fatal. Nerve cells in the spinal cord die, eventually taking away a person's ability to move or even breathe. A consortium of ALS researchers at multiple institutions, including Sanford-Burnham Medical Research Institute, Brigham and Women's Hospital, and the University of Massachusetts Medical School, tested transplanted neural stem cells as a treatment for the disease. In 11 independent studies, they found that transplanting neural stem cells into the spinal cord of a mouse model of ALS slows disease onset and progression. This treatment also improves host motor function and significantly prolongs survival. The transplanted neural stem cells did not benefit ALS mice by replacing deteriorating nerve cells. Instead, neural stem cells help by producing factors that preserve the health and function of the host's remaining nerve cells. They also reduce inflammation and suppress the number of disease-causing cells in the host's spinal cord. These findings, published December 19 in Science Translational Medicine, demonstrate the potential neural stem cells hold for treating ALS and other nervous system disorders.

"While not a cure for human ALS, we believe that the careful transplantation of neural stem cells, particularly into areas that can best sustain life--respiratory control centers, for example--may be ready for clinical trials," Evan Y. Snyder, M.D., Ph.D., director of Sanford-Burnham's Stem Cell and Regenerative Biology Program and senior author of the study.

Neural stem cells

In this study, researchers at multiple institutions conducted 11 independent studies to test neural stem cell transplantation in a well-established mouse model of ALS. They all found that this cell therapy reduced the symptoms and course of the ALS-like disease. They observed improved motor performance and respiratory function in treated mice. Neural stem cell transplant also slowed the disease's progression. What's more, 25 percent of the treated ALS mice in this study survived for one year or more--roughly three to four times longer than untreated mice.

Neural stem cells are the precursors of all brain cells. They can self-renew, making more neural stem cells, and differentiate, becoming nerve cells or other brain cells. These cells can also rescue malfunctioning nerve cells and help preserve and regenerate host brain tissue. But they've never before been studied extensively in a good model of adult ALS.

How neural stem cells benefit ALS mice

Transplanted neural stem cells helped the ALS mice, but not for the obvious reason--not because they became nerve cells, replacing those missing in the ALS spinal cord. The biggest impact actually came from a series of other beneficial neural stem cell activities. It turns out neural stem cells produce protective molecules. They also trigger host cells to produce their own protective molecules. In turn, these factors help spare host nerve cells from further destruction.

Then a number of other positive events take place in treated mice. The transplanted normal neural stem cells change the fate of the host's own diseased neural stem cells--for the better. This change decreases the number of toxin-producing, disease-promoting cells in the host's spinal cord. Transplanted neural stem cells also reduce inflammation.

"We discovered that cell replacement plays a surprisingly small role in these impressive clinical benefits. Rather, the stem cells change the host environment for the better and protect the endangered nerve cells," said Snyder. "This realization is important because most diseases are now being recognized as multifaceted in their cause and their symptoms--they don't involve just one cell type or one malfunctioning process. We are coming to recognize that the multifaceted actions of the stem cell may address a number of these disease processes."
-end-
This research was funded by Project ALS, California Institute for Regenerative Medicine, the U.S. National Institutes of Health (National Institute of Neurological Disorders and Stroke grants R21NS053935, 1RC2NS070342-01, 1RC1NS068391-01, R01NS050557-05, U01NS05225-03), U.S. Department of Veterans Affairs, Christopher Reeve Foundation/American Paralysis Association, Sanford Children's Health Research Center, Zinberg Foundation, ALS Therapy Alliance, ALS Association, Angel Fund, Al-Athel Foundation, Pierre L. deBourgknect ALS Research Foundation, P2ALS, and HeadNorth.

The study was co-authored by Yang D. Teng, Brigham and Women's Hospital, Harvard Medical School, Veterans Affairs Boston Healthcare System; Susanna C. Benn, Massachusetts General Hospital; Steven N. Kalkanis, Harvard Medical School, Massachusetts General Hospital; Jeremy M. Shefner, State University of New York, Syracuse; Renna C. Onario, Harvard Medical School, Veterans Affairs Boston Healthcare System, Children's Hospital-Boston; Bin Cheng, Columbia University; Mahesh B. Lachyankar, Harvard Medical School, Children's Hospital-Boston; Michael Marconi, Children's Hospital-Boston, Beth Israel Deaconess Medical Center; Jianxue Li, Beth Israel Deaconess Medical Center; Dou Yu, Harvard Medical School, Veterans Affairs Boston Healthcare System; Inbo Han, Harvard Medical School, Veterans Affairs Boston Healthcare System; Nicholas J. Maragakis, Johns Hopkins University; Jeronia Lládo, Johns Hopkins University; Kadir Erkmen, Harvard Medical School, Children's Hospital-Boston; D. Eugene Redmond Jr., Yale University School of Medicine; Richard L. Sidman, Harvard Medical School, Beth Israel Deaconess Medical Center; Serge Przedborski, Columbia University; Jeffrey D. Rothstein, Johns Hopkins University; Robert H. Brown Jr., Massachusetts General Hospital, University of Massachusetts Medical School; Evan Y. Snyder, Harvard Medical School, Children's Hospital-Boston, Beth Israel Deaconess Medical Center, and Sanford-Burnham Medical Research Institute.

About Sanford-Burnham Medical Research Institute
Sanford-Burnham Medical Research Institute is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. The Institute consistently ranks among the top five organizations worldwide for its scientific impact in the fields of biology and biochemistry (defined by citations per publication) and currently ranks third in the nation in NIH funding among all laboratory-based research institutes. Sanford-Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Sanford-Burnham is a U.S.-based, non-profit public benefit corporation, with operations in San Diego (La Jolla), California and Orlando (Lake Nona), Florida. For more information, news, and events, please visit us at sanfordburnham.org.

Sanford-Burnham Prebys Medical Discovery Institute

Related Stem Cell Articles from Brightsurf:

Fat cell hormone boosts potential of stem cell therapy
Mesenchymal stem cell (MSC) therapy has shown promising results in the treatment of conditions ranging from liver cirrhosis to retinal damage, but results can be variable.

Oncotarget Characterization of iPS87, a prostate cancer stem cell-like cell line
Oncotarget Volume 11, Issue 12 reported outside its natural niche, the cultured prostate cancer stem cells lost their tumor-inducing capability and stem cell marker expression after approximately 8 transfers at a 1:3 split ratio.

Stem cell identity unmasked by single cell sequencing technology
Scientists from The University of Queensland's Diamantina Institute have revealed the difference between a stem cell and other blood vessel cells using gene-sequencing technology.

It's all about the (stem cell) neighborhood
Researchers at Duke-NUS Medical School have now identified how the stem cell neighbourhood, known as a niche, keeps stem cells in the gut alive.

Spaceflight activates cell changes with implications for stem cell-based heart repair
A new study of the effects of spaceflight on the development of heart cells identified changes in calcium signaling that could be used to develop stem cell-based therapies for cardiac repair.

Not just a stem cell marker
The protein CD34 is predominantly regarded as a marker of blood-forming stem cells but it helps with migration to the bone marrow too.

Interferon-beta producing stem cell-derived immune cell therapy on liver cancer
Induced pluripotent stem (iPS) cell-derived myeloid cells (iPS-ML) that produce the anti-tumor protein interferon-beta (IFN-beta) have been produced and analyzed by researchers from Kumamoto University, Japan.

Scientists aim to create the world's largest sickle cell disease stem cell library
Scientists at the Center for Regenerative Medicine at Boston Medical Center and Boston University School of Medicine are creating an induced pluripotent stem cell (iPSC)-based research library that opens the door to invaluable sickle cell disease research and novel therapy development.

Designer switches of cell fate could streamline stem cell biology
Researchers at the University of Wisconsin-Madison have developed a novel strategy to reprogram cells from one type to another in a more efficient and less biased manner than previous methods.

Allen Institute for cell science releases gene edited human stem cell lines
The Allen Institute for Cell Science has released the Allen Cell Collection: the first publicly available collection of gene edited, fluorescently tagged human induced pluripotent stem cells that target key cellular structures with unprecedented clarity.

Read More: Stem Cell News and Stem Cell 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.