From bone marrow to brain: stem cells in neuroprotection, plasticity, and neuroregeneration

At present, curative therapies for neurological diseases are limited, even though they are prevalent worldwide. So far, molecular strategies developed for brain disorders act through one single molecular mechanism, yet, these diseases are multifactorial and highly complex, as to why a successful therapy likely calls for a more multifaceted and cell-based approach. The bone marrow contains a mixed stem and progenitor cell population including hematopoietic stem cells (HSC) and mesenchymal stromal stem cells (MSC), which are potential endogenous candidates for cell-based therapy in various brain disorders like stroke, trauma, and neurodegeneration. Unlike the neural stem cells (NSC), bone marrow HSC are readily isolated, mobilized and expanded by means of treatment with granulocyte-colony stimulating factor (G-CSF) and CXCR4-antagonist plerixafor. Once in the blood circulation, the cells preferentially home to injured tissues including the brain. Bone marrow cells may convey neuroprotection, plasticity, and neuroregeneration by different mechanisms of action, which include either transdifferentiation or cell-cell fusion with resident brain cells. Bone marrow cells also benefit the injured brain by secreting bioactive factors, which in a paracrine manner convey intrinsic repair and enhance neurogenesis. Furthermore, transplanted MSC may activate the astrocytes leading to increased glial secretion of neurotrophic growth factors and enhanced proliferation and migration of the resident NSC. These neuroregenerative mechanisms of action are not mutually exclusive, in fact they may provide a multifaceted therapeutic approach, which is requested in order to move neurorestorative and protective strategies into the clinic. Biomedical Reviews 2011; 22: 1-6.