Replacement of "fault cleaners" in the brain. Fudan Pengbo team developed three solutions

In the latest issue of Cell Reports, a team from Fudan University School of Medicine's Institute for Brain Science Translation reported on three new options they have developed that have enabled the efficient replacement of a class of faulty brain cells, microglia, in adult animals.
Given that the failure of these cells is related to the occurrence and development of a variety of neurological diseases, including Alzheimer's disease, amyotrophic lateral sclerosis, parkinson's disease, the researchers believe that this advance in research will provide new ideas and solutions for the treatment of related diseases, and that the respective advantages and applicable scenarios of the three options will provide a variety of options for future clinical treatment.
glial cells are a special class of immune cells distributed in the central nervous system, including the brain, spinal cord and retina.
glial cells act like "cleaners" in the brain, helping to remove "junk" from the central nervous system, such as amyloid proteins closely associated with Alzheimer's disease.
, however, there has been a lot of scientific evidence in recent years that when these cells fail, such as carrying disease-caused genetic mutations, they change from "cleaners" to "neuron killers" that trigger nerve inflammation.
it is assumed that genetic therapy could alleviate or even eliminate these diseases by replacing defective genes in small glial cells with functional genes.
, however, the researchers point out that due to the limitations of viral vectors, current methods make it difficult to manipulate small glial cells throughout the brain, becoming an application bottleneck for gene therapy.
replacing proto-glial cells with transplantation of bone marrow cells or exogenetic small glial cells is another treatment idea.
But results in animal experiments have shown that replacement efficiency is less than 2%, or must be replaced in specific genetically modified animals (and must be replaced early in development), thus limiting the clinical application of such strategies.
study, professor Pember led the team to challenge the challenge of small glial cell replacement.
previous work, they found that when drugs were used to eliminate existing small glial cells, the few remaining small glial cells had amazing potential for self-renewal.
, on this basis, the team developed three different types of small glial cell replacement schemes.
specifically, the researchers first used a drug to efficiently remove small glial cells from the central nervous system in adult mice without causing significant side effects.
, external bone marrow cells are introduced through bone marrow transplantation.
These bone marrow cells can enter the brain and differentiate into small glial cell-like cells, replacing more than 92 percent more efficiently in the brain, while in the retina and spinal cord, more than 99 percent and 93 percent of small glial cells are replaced by exogenous cells, respectively.
this option replaced the original glial cells with bone marrow transplants with extremely high replacement effects, so the researchers named them mrBMT (microglia replacement by bone marrow transplantation).
Taking into account that the donor cells used by mrBMT are bone marrow cells, and that bone marrow cells are donated from very limited sources, the Pember team has further developed a second small glial cell replacement solution to induce differentiation into small glial cell-like cells with easier access and a longer number of blood cells.
the program, named mrPB (microglia replace by permite blood), is also more than 80% efficient in replacing native glial cells.
In certain cases, patients may only need to replace faulty glial cells in specific areas of the brain, without involving other brain regions, so in a third scenario, mrMT, the researchers transplanted normal glial cells from an external source to a specific local brain region to replace the faulty cells.
in contrast, the small glial cells produced by mrBMT and mrPB were still nuanced from normal small glial cells, while in the third scenario, the transplanted cells retained the characteristics of small glial cells completely. The
team concluded that these three new small glial cell replacement options are the first to effectively replace small glial cells within the central nervous system or specific brain regions, and the first to achieve large-scale cell transplantation within the central nervous system.
" have their own advantages and limitations, but each is more suitable for different scenarios.
all three options will open up new avenues for treating neurological diseases associated with small glial cells, " says Professor Pember.
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