Stem Cell Attractants in Multiple Sclerosis Brains
For stem cells to mediate their effects they must either be placed locally at the point of damage, or they must find their way there. One of the questions that people ask is “how can intravenously administered stem cells home to where they need to go?” To answer this, lets first think about the stem cell therapy that has been used for more than 4 decades: bone marrow transplantation.
In bone marrow transplantation the stem cells are injected intravenously into the recipient. So how do they find their way to the bone marrow? One of the may ways that this occurs is because the bone marrow expresses a protein called stromal derived factor (SDF)-1, which is also known as CXCL-12. Specifically, bone marrow stromal cells are known to constitutively make this protein, which is what keeps the hematopoietic stem cells in the bone marrow. So when donor hematopoietic stem cells are injected into a recipient, they selectively home to the bone marrow because of expression of SDF-1. We know that SDF-1 is important for this process because if you block the interaction of SDF-1 with its receptor on the stem cell, called CXCR4, in a healthy person, then the healthy person’s bone marrow stem cells enter the blood. The clinically used stem cell mobilizer mozobil works by interrupting this pathway.
We also know that SDF-1 is important for attracting stem cells because after heart attacks, this protein is produced by the injured heart muscle in large quantities, which attracts the patient’s own bone marrow cells to the area of injury.
A recently published study (McCandless et al. IL-1R Signaling within the Central Nervous System Regulates CXCL12 Expression at the Blood-Brain Barrier and Disease Severity during Experimental Autoimmune Encephalomyelitis. J Immunol. 2009 Jun 17) demonstrates that SDF-1 is expressed during the initial phases of disease progression in the mouse model of multiple sclerosis.
This study may provide one important clue as to how stem cells home into the central nervous system of patients with multiple sclerosis. However this is a controversial area since, although mesenchymal stem cells prevent disease in animal models, some studies suggest that the stem cells do not need to actually home to the area of injury to inhibit multiple sclerosis, but instead may do this through immune modulation.