A therapeutic technique to transplant blood-forming (hematopoietic) stem cells directly into the brain that could herald a revolution in the approach to treating central nervous system diseases and neurodegenerative disorders has been developed by the researchers at Children's Hospital Boston. The technique could be used to transplant donor-matched hematopoietic stem cells (HSCs) or a patient's own genetically-engineered HSCs into the brain. In their study, the team tested the technique in a mouse model to treat lysosomal storage disorders, a group of severe metabolic disorders that affect the central nervous system. 

The team's findings are groundbreaking because, until now, it was thought that HSCs - from a healthy, matched donor or a patient's own genetically-corrected cells - needed to be transplanted indirectly, through an intravenous line to the bloodstream. Therapeutic success has then depended on those cells engrafting in a patient's bone marrow, maturing and naturally circulating into the brain, at a very slow and inefficient rate.

But in children with lysosomal storage disorders, caused by enzyme imbalances that result in a dangerous build-up of lipids, carbohydrates or other materials in the body's cells, time is of the essence to stop the disease's progression. The main issue with the conventional HSC transplant strategy has been the length of time needed for the therapy to take effect in the brain. It can take up to a year for the genetically-engineered cell lineage to proliferate, spread and produce therapeutic effects in the brain - oftentimes, patients don't have the luxury of time to wait.

The researchers wanted to find a faster and more direct way to transplant therapeutic HSCs into the brain. Once the genetically-engineered HSCs are transplanted into the brain's ventricles, the crucial enzyme they contain helps to metabolize the materials that were previously building up and causing tissue damage. A new lineage of cells descended from the transplanted HSCs - a type of cell called a myeloid - begin to scavenge and consume the excess material that is responsible for neurodegeneration.

There's a positive impact from the presence of the new, metabolically-functional myeloid cells because they release signaling cytokines that counteract neuroinflammation, which if unchecked can trigger neuronal damage. Importantly, the transplanted HSCs engraft in the mouse brains without migrating to other areas of the central nervous system. This essentially could create a chimera - a separate genetic profile within an organism - within the brain. The ability to engineer a chimeric population of brain cells could open powerful new avenues for preventing or reversing neurodegenerative diseases