Scientists prove it is possible to replace sick human cells with healthy ones, a discovery that could allow damaged or lost brain cells to be replaced

A significant breakthrough has been made in the field of cell replacement therapies for neurological and psychiatric disorders, according to recent research published in the journal Nature Biotechnology.

The study, conducted by Professor Steve Goldman and his team at the University of Rochester Medical Center, sheds light on the viability of using healthy cells to replace diseased and aging cells in the central nervous system, particularly glial cells associated with conditions such as Huntington’s disease, amyotrophic lateral sclerosis (ALS), and schizophrenia.

Lead author of the study, Dr. Steve Goldman, MD, PhD, a professor of Neurology at the University of Rochester Medical Center (URMC), stated, “A broad variety of disorders we associate with neuronal loss now appear to be caused by dysfunctional glial cells.

“This makes these diseases attractive targets for stem and progenitor cell-based therapies.”

The study, conducted at the URMC Center for Translational Neuromedicine under the co-direction of Dr. Goldman, elucidates the competitive interactions among human glial progenitor cells—precursor cells capable of generating both astrocytes and oligodendrocytes, the major types of glial cells—in the adult brain. Moreover, the research highlights the advantage that young and healthy cells possess over their aged and diseased counterparts.

The culmination of a decade of scientific progress underlies these groundbreaking findings. In 2013, Dr. Goldman and his team introduced strategies for deriving glial support cells from embryonic stem cells. Subsequently, they transplanted these cells into the brains of infant mice, leading to the creation of human glial-chimeric mice—an impressive technical achievement enabling the study of human glial cells within a living brain. The researchers observed that after transplantation, human glial progenitor cells outcompeted the native cells, resulting in brains consisting of mouse neurons and human glia.

Further experiments involved transplanting human glial cells carrying the Huntington’s disease (HTT) mutation. These investigations revealed that the mutation impeded the functionality of glial progenitor cells, thereby impairing the production of healthy astrocytes and oligodendrocytes. The team also demonstrated that transplanting healthy human glial progenitor cells into mouse models of Huntington’s disease delayed the progression of the disease, highlighting the crucial role of glial dysfunction in this untreatable neurodegenerative disorder.

While the previous studies were confined to transplanting human cells into mouse brains, the recent Nature Biotechnology study indicates that transplanting human cells into another human brain could yield similar benefits. It underscores the potential value of cell replacement therapies by illustrating that healthy human glia can outcompete and replace diseased human cells.

To demonstrate this phenomenon, the researchers initially implanted human glial progenitor cells with the HTT mutation into the brains of newborn mice. Upon reaching adulthood, the researchers subsequently transplanted healthy human glial cells, which successfully displaced and eliminated the counterparts carrying the Huntington’s disease mutation.

“In the striatum, our target area, the healthy cells essentially kicked out the disease cells, eventually replacing the glial progenitor population entirely,” explained Dr. Goldman.  “You can actually see a wave of migration and a border where the cells expressing the HTT mutation are dying off and being replaced by heathy ones.

In a related set of experiments, the team discovered that younger and healthy human glial progenitors outperformed older but otherwise healthy human glia, indicating that cellular youth is a critical factor in competitive success.

“These findings have strong therapeutic implications, as they suggest that in the adult human brain, resident glia–whether diseased or simply aged—may be replaced following the introduction of younger and healthier cells,” emphasized Dr. Goldman.

Source: 10.1038/s41587-023-01798-5

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