Multiple sclerosis (MS) is caused when the immune system destroys the myelin insulation around nerve fibres in the central nervous system (CNS). Now, scientists at the University of Bonn have genetically engineered bone marrow cells that can both treat MS by reducing inflammation and clearing tissue debris and could also be used to deliver drugs that promote nerve repair. The loss of myelin, coupled with inflammation and scarring (sclerosis) disrupts nerve signals causing weakness or paralysis of the limbs, balance and coordination difficulties and other symptoms. There is currently no cure for MS, although drugs that modulate the immune system can slow its progression. Before the damage caused by MS can be repaired, the cellular debris must be cleared and inflammation needs to be reduced. Even so, drugs to promote nerve and myelin repair must be able to cross the barrier that protects the CNS, which is difficult for larger molecules and could require a drug delivery vehicle to succeed. Harald Neumann and his colleagues realised that bone marrow cells called myeloid precursor cells could be the answer because they naturally migrate into the CNS and can form microglia, which act as immune cells for the CNS and could clear the debris. Microglia also produce a protein called trigger receptor expressed on myeloid cells-2 (TREM2). The scientists collected myeloid precursor cells from mouse bone marrow and modified it to produce TREM2. These cells were then injected into mice with experimental autoimmune encephalomyelitis (EAE), which is used as an animal model for MS. Normal myeloid precursor cells were also injected as a control. In healthy mice or those only just beginning to show symptoms of EAE, neither cell type migrated to the spinal cord. However, when EAE symptoms were at their peak, both sets of myeloid precursor cells migrated into the mice' spinal cords where the TREM2-producing cells reduced nerve damage and halted myelin loss. The therapeutic cells also increased the amount of debris cleared, and an anti-inflammatory environment was created. This was shown by increased levels of interleukin-10 (IL-10), a human cytokine that prevents the production of pro-inflammatory cytokines such as Interferon-gamma, IL-2, IL-3, TNF-alpha and GM-CSF. However, in an article detailing the results in PLoS Medicine the researchers admit that although increased IL-10 levels might be due to the TREM2-modified cells, "we cannot exclude the possibility that TREM2-transduced myeloid precursors act indirectly via a secondary immune organ to stimulate a regulatory immune cell type migrating into the CNS". The authors go on to explain that IL-10 helps regulate the immune system and is vital for the recovery phase of EAE; remission has been shown to be impaired in IL-10-deficient mice (as previously reported by scientists at Harvard Medical School). "TREM2-transduced myeloid precursor cells applied intravenously ameliorate EAE either locally inside the CNS or indirectly via another regulatory immune cell type by clearance of tissue debris and resolution of inflammation, thereby opening new avenues for cell therapy of inflammatory and degenerative CNS diseases," the authors conclude.