City of Hope's Yanhong Shi, Ph.D., and her colleagues engineered healthy human skin cells containing the functional aspartoacylase (ASPA) gene into induced pluripotent stem cells (iPSCs) and then differentiated the iPSCs into oligodendroglial progenitor cells, the precursor cells that produce myelin, an insulating sheath that wraps around nerve fibers. Like a bullet train, myelin sheaths facilitate the light-speed transport of information along neuronal axons.
Newswise — City of Hope, a renowned institution dedicated to cancer research and treatment, as well as the study of diabetes and other serious ailments, has made a groundbreaking discovery. Their team of scientists has successfully created universal donor stem cells, holding tremendous potential for future therapies. These stem cells offer the possibility of life-saving treatment for children afflicted with devastating brain disorders like Canavan disease. Moreover, they may hold promise for individuals suffering from degenerative conditions such as Alzheimer's and multiple sclerosis. The findings of this remarkable study were recently published in the esteemed journal Advanced Science.
Yanhong Shi, Ph.D., who holds the position of Chair in the Department of Neurodegenerative Diseases and is the esteemed Herbert Horvitz Professor in Neuroscience at Beckman Research Institute of City of Hope, expressed the potential of City of Hope's innovative approach. He highlighted that the "off-the-shelf" nature of their methodology can be extended to enhance the quality of life for cancer patients who experience cognitive impairment or impaired motor function as a result of chemotherapy or radiation treatment. Dr. Shi, who has dedicated 12 years to this research, emphasizes the far-reaching applications of this breakthrough.
SIGNIFICANCE
According to Dr. Yanhong Shi, this groundbreaking achievement represents the first instance of engineering stem cells to function as universal donors specifically for cell therapy aimed at central nervous system diseases. This "off-the-shelf" strategy holds tremendous potential by enabling patients in need of cell therapy to receive life-saving treatments much earlier, potentially reducing the wait time by three to six months. The significance of this advancement cannot be overstated, as it has the potential to revolutionize the field of cell therapy and significantly improve patient outcomes.
BACKGROUND
Under the guidance of Dr. Yanhong Shi, her team of researchers successfully employed a method involving the genetic engineering of healthy human skin cells. Specifically, they integrated the functional aspartoacylase (ASPA) gene into induced pluripotent stem cells (iPSCs). These iPSCs were then transformed into oligodendroglial progenitor cells, which are the precursor cells responsible for generating myelin. Myelin plays a vital role in the nervous system by serving as an insulating sheath that envelops nerve fibers. Analogous to a high-speed train, these myelin sheaths enable the rapid transmission of information along neuronal axons.
The Canavan disease animal models subjected to treatment demonstrated elevated ASPA function in comparison to the control mice and experienced a decrease in the detrimental buildup of the metabolite N-acetyl-L-aspartate (NAA) in the brain. Excessive NAA levels have been associated with compromised motor capabilities, cognitive impairments, and premature mortality. Consequently, the treated mice displayed enhanced myelination and significantly enhanced motor abilities. Significantly, the universally donated cells successfully evaded immune assault from the recipient mice.
Although the prior method devised by her team entailed generating a cell therapy using the patient's own cells to circumvent immune rejection, this novel strategy employed techniques enabling the transplantation of engineered hypoimmunogenic cells from a healthy donor into a humanized disease model, without triggering the immune system's response to eliminate the foreign therapeutic.
FUNDING
The study was supported by the California Institute for Regenerative Medicine (TRAN1-08525), the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (NIH) (U01 NS122101), and the National Cancer Institute of the NIH (P30CA33572).
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