Scientists at City of Hope have achieved a groundbreaking milestone in stem cell research, developing universal donor stem cells that hold the potential to save the lives of children suffering from fatal brain conditions like Canavan disease. Furthermore, these engineered cells offer hope for individuals with degenerative diseases such as Alzheimer’s and multiple sclerosis. The study, published in Advanced Science, showcases the transformative impact of this novel approach.

Dr. Yanhong Shi, Chair of the Department of Neurodegenerative Diseases and the Herbert Horvitz Professor in Neuroscience at Beckman Research Institute of City of Hope, explains that the off-the-shelf strategy employed by City of Hope can be expanded to enhance the quality of life for cancer patients facing cognitive impairment or motor function issues resulting from chemotherapy or radiation. Dr. Shi has dedicated 12 years to this groundbreaking research.

This pioneering endeavor marks the first time that stem cells have been genetically engineered to serve as universal donors for cell therapy targeting central nervous system diseases. The off-the-shelf approach offers a remarkable advantage, providing life-saving treatments to patients three to six months earlier. Dr. Shi and her team successfully converted healthy human skin cells, containing the functional aspartoacylase (ASPA) gene, into induced pluripotent stem cells (iPSCs). These iPSCs were then differentiated into oligodendroglial progenitor cells, which are precursor cells responsible for producing myelin—a protective sheath enveloping nerve fibers. Similar to a bullet train, myelin sheaths facilitate the rapid transmission of information along neuronal axons.

In animal models with Canavan disease, the treated mice exhibited increased ASPA activity compared to the control group. Additionally, they demonstrated a reduction in the toxic accumulation of the metabolite N-acetyl-L-aspartate (NAA) in the brain. Excessive levels of NAA have been linked to impaired motor function, cognitive deficiencies, and premature death. As a result of the treatment, the mice showed improved myelination and significantly enhanced motor function. Notably, the universal donor cells successfully evaded immune rejection by the recipient mice.

Previously, Dr. Shi’s team developed a cell therapy technique that utilized a patient’s own cells to avoid immune rejection. However, this innovative approach involves the use of engineered hypoimmunogenic cells derived from healthy donors. These cells can be transplanted into humanized disease models without triggering an immune response that would typically eliminate foreign therapeutic agents.

The development of universal donor stem cells represents a major breakthrough in the field of regenerative medicine, offering hope to patients affected by devastating neurological disorders. With continued advancements, these off-the-shelf therapies may revolutionize treatment timelines and improve the lives of countless individuals battling debilitating diseases of the central nervous system.

By Impact Lab