New universal donor stem cell therapy to treat degenerative brain diseases

The researchers believe that this therapy could one day be applied to children with fatal brain conditions.
Sejal Sharma
Representational image
Representational image


Demyelinating diseases, one of the most debilitating diseases in neurology, are caused by damage to the protective covers surrounding our nerve fibers in the brain. These protective coverings are called myelin.

In a study published in Advanced Science, scientists have claimed to develop universal donor stem cells that could help in the restoration of myelin in demyelinated brains.

Of the many demyelinating diseases, the study provides a therapeutic candidate for the Canavan disease (CD). It is a severe, progressive genetic disease that has no cure.

In a first-of-its-kind study, the researchers engineered the stem cells to become universal donors for cell therapy, which would help target diseases of the central nervous system.

As per the City of Hope’s press release, the team engineered oligodendroglial progenitor cells (OPCs), which are the precursor cells that produce myelin.

The study was conducted in an animal model. The hypoimmunogenic OPCs were transplanted into the brains of mice with CD. The transplanted OPCs could survive well and migrate widespread into the whole brain. The team found that the treated mice exhibited increased myelination and showed improvement in its motor function. Importantly, the universal donor cells were able to evade immune attack from the recipient mice.

Dr Yanhong Shi, who has been working on this research for 12 years, said that this “off-the-shelf” approach can provide patients who need cell therapy with lifesaving treatments three to six months earlier.

“The off-the-shelf approach City of Hope is taking can easily be extended to improve the quality of life of cancer patients who are experiencing cognitive impairment or impaired motor function as a side effect of chemotherapy or radiation,” she added.

The researchers believe that this therapy could one day be applied to children with fatal brain conditions as well as to people with other degenerative diseases, such as Alzheimer’s and multiple sclerosis.

The City of Hope is a Cancer treatment and research center in the U.S. It is also a leading research center for diabetes and other life-threatening illnesses.

Study abstract:

Demyelinating disorders are among the most common and debilitating diseases in neurology. Canavan disease (CD) is a lethal demyelinating disease caused by mutation of the aspartoacylase (ASPA) gene, which leads to the accumulation of its substrate N-acetyl-l-aspartate (NAA), and consequently demyelination and vacuolation in the brain. In this study, hypoimmunogenic human induced pluripotent stem cell (iPSC)-derived oligodendrocyte progenitor cells (OPC) are developed from a healthy donor as an “off-the-shelf” cell therapy. Hypoimmunogenic iPSCs are generated through CRISPR/Cas9 editing of the human leukocyte antigen (HLA) molecules in healthy donor-derived iPSCs and differentiated into OPCs. The OPCs are engrafted into the brains of CD (nur7) mice and exhibit widespread distribution in the brain. The engrafted OPCs mature into oligodendrocytes that express the endogenous wildtype ASPA gene. Consequently, the transplanted mice exhibit elevated human ASPA expression and enzymatic activity and reduced NAA level in the brain. The transplanted OPCs are able to rescue major pathological features of CD, including defective myelination, extensive vacuolation, and motor function deficits. Moreover, the hypoimmunogenic OPCs exhibit low immunogenicity both in vitro and in vivo. The hypoimmunogenic OPCs can be used as “off-the-shelf” universal donor cells to treat various CD patients and many other demyelinating disorders, especially autoimmune demyelinating diseases, such as multiple sclerosis.

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