A new discovery increases the likelihood that treatments could eventually boost specific subtypes of stem cells, and promote self healing following injury or disease. In response to tissue injury or disease, progenitor cells are mobilised from bone marrow into the tissues and contribute to tissue repair and regeneration. Different subpopulations of progenitor cells are recruited depending on the type and site of disease or tissue injury. Although it is becoming apparent that specific types of progenitor cells could be used to treat a variety of diseases, there are practical and technical difficulties in harvesting, isolation, ex vivo expansion, and delivery of these cells. An alternative strategy would be to directly stimulate the mobilisation of specific populations of stem cells from the bone marrow into the circulation. Scientists at Imperial College, London, have shown that the mobilisation of progenitor cell subsets can be differentially regulated by growth factors that affect their retention in bone marrow and cell-cycle status. Treatment of mice with granulocyte colony-stimulating factor (G-CSF) followed by the CXCR4 antagonist, Mozobil™ (AMD3100), caused maximal mobilisation of hematopoietic stem cells (HPCs) and neutrophils. On the other hand, treatment with vascular endothelial growth factor (VEGF) followed by Mozobil™ maximally stimulated mobilisation of endothelial progenitor cells (EPCs) and stromal progenitor cells (SPCs). By showing that different factors and molecular mechanisms regulate the mobilisation of discrete populations of progenitor cells from the bone marrow, the study has far reaching implications for regenerative medicine. Although it is not yet clear whether such an approach would, for example, speed cardiac repair following myocardial infarction or promote bone healing after a fracture, the ability to selectively mobilise different stem cell populations will enable further research in these areas. The study is published in full in the January 9th issue of Cell Stem Cell.
New Indications for AMD-3100
A drug which failed to reach the market as a treatment for HIV/AIDS has recently been shown to improve the survival of mice infected with West Nile virus, a virus that can cause encephalitis. It is believed that the drug, AMD-3100, acts by allowing T-cells to cross the blood-brain barrier and combat virus infecting the brain.
The drug works by blocking the receptor for the chemokine, CXCR4, and was originally developed to prevent the syncytium-forming variant of HIV using this receptor to gain entry to cells. Clinical trials, however, failed to show robust anti-viral activity.
The CXCR4 receptor and its physiological ligand, SDF-1, are also involved in mobilisation of hematopoietic stem cells into the bloodstream. Genzyme has recently filed applications in the US and Europe for AMD-3100 (Mozobil™, plerixafor) to enhance mobilization of hematopoietic stem cells for collection and subsequent autologous transplantation in patients with lymphoma and multiple myeloma. Because patients receive high-dose chemotherapy, which destroys bone marrow, a stem cell transplant is needed after chemotherapy to replenish blood-forming bone marrow cells. Genzyme has been developing Mozobil since its acquisition of AnorMED in 2006.