December 6, 2023

The researchers transplanted cells capable of forming specialized brain support cells into the brains of mice and found that they not only outcompeted and replaced unhealthy cells, but also outcompeted and replaced aging cells. These findings open the door to the development of effective treatments for a range of diseases including multiple sclerosis, ALS, Alzheimer’s disease, autism and schizophrenia.

“Glial cells” is a general term for cells that support the nerve cells (neurons). Progenitor cells are descendants of stem cells that can differentiate into specific cell types. In the case of glial cells, human glial progenitor cells (hGPCs) differentiate into subtypes, including astrocytes and oligodendrocytes, specialized for specific functions.

Astrocytes make up the majority of our central nervous system cells, providing support and protection to neurons, transporting nutrients and removing waste. Oligodendrocytes deposit and maintain a lipid-rich insulating wrap called myelin around some axons, the part of a neuron that connects with another neuron and allows the transmission of nerve impulses.

Dysfunctional astrocytes and oligodendrocytes are associated with a variety of neurodegenerative and neuropsychiatric diseases. Given hGPCs’ ability to generate new astrocytes and oligodendrocytes, researchers at the University of Copenhagen in Denmark investigated how transplanting healthy hGPCs could help restore brain function.

Researchers have previously demonstrated that healthy human glial cells replace unhealthy mouse glial cells when transplanted into a mouse model with Huntington’s disease, a rare and fatal genetic disorder that causes progressive neuronal failure.

In the current study, they wanted to see if healthy human cells could replace diseased human cells. So they introduced healthy hGPCs into “chimeric” mice that had been injected with human stem cells from people with Huntington’s disease. The researchers found that the healthy cells replaced and completely replaced the diseased cells.

“We transplanted healthy human cells into mice that were ‘humanized’ with glial cells expressing the Huntington mutation, and the healthy glial cells outcompeted and replaced the diseased glial cells, virtually eliminating the diseased glial cell population,” said Steven Goldman, corresponding author of the study.

Interestingly, the researchers found that when young donor hGPCs were introduced into the brains of humanized mice, they outcompeted and replaced healthy, non-diseased but aged cells. The researchers say their finding that healthy hGPCs replace diseased and aging cells is significant and highlights the potential for developing treatments that could be used in a wide range of scenarios.

“What this tells us is that it’s not just a matter of healthy cells overcoming Huntington’s diseased cells, but that it has a much broader range of potential uses because we can study a variety of disease targets with aged or diseased glial cell populations,” Goldman said. “The advantages are significant in terms of where it’s going, because glial cells are involved in a variety of diseases.”

Glial cells are critical for the development of certain neuropathologies. The neurodegenerative disease amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, epilepsy, multiple sclerosis (MS), Parkinson’s disease, and Alzheimer’s disease, is associated with dysfunctional glial cells. The same goes for neuropsychiatric disorders, autism spectrum disorder (ASD), bipolar disorder, and schizophrenia.

“If we can replace diseased and aged cells, then we should be able to restore normal function in these degenerative diseases, as we’ve seen in experimental models of Huntington’s disease,” Goldman said. “But it’s basically a proof of principle, because we think the same approach works for some other diseases. In ALS, there’s some frontotemporal dementia, and even some hereditary schizophrenia, as well as myelin disorders and age-related white matter loss.”

The researchers propose a clinical trial to test the effectiveness of hGPC transplantation for Huntington’s disease and two other diseases: primary progressive multiple sclerosis (PPMS) and Pelizaus-Metzbach disease (PMD). Most people with MS go through periods of relapses and remissions, whereas about 15 percent have PPMS, a disease that keeps getting worse without periods of remission. PMD is a rare, progressive genetic disorder that damages oligodendrocytes, leading to deterioration of coordination, motor ability, and cognitive function.

The researchers hope to conduct human clinical trials within the next few years.

“Things are pretty remote,” Goldman said. “We still need to be absolutely sure about the long-term safety of transplanted cells. But we expect to have those data in about a year and a half. By then, we hope to be able to get approval to go into patients, so I hope we can start trials of this approach within two years.”

The study was published in the journal natural biotechnology.

source: University of Copenhagen pass Urik Alert!