Immunomodulation by Stem Cells and Hematopoietic Growth Factors for Neurorestoration

Abstract

The immune response to grafted tissue is complex, but is dependent on a number of variables, which include the phylogenetic relationship of donor tissue to host and its composition and mode of implantation. After transplants in brain, the rejection process has both a cellular and humoral component. However, certain types of stem cells, especially mesenchymal stem cells and neural stem cells or neural precursor cells might also have immunomodatory effects in the injured brain. They can release soluble molecules such as cytokines and chemokines and express immune-relevant receptors such as chemokine receptors and cell adhesion molecules, which are able to profoundly change inflammatory environments. Granulocyte-colony stimulating factor (G-CSF) has immunomodulatory effects. In vivo administration of G-CSF in both animal models and humans has concordantly shown immunomodulatory effects such as suppressing the production of proinflammatory cytokines in peripheral blood mononuclear cells, inducing tolerant dendritic cells, and enhancing interleukin-4 but reducing interferon and production in lymphocytes. Erythropoietin (EPO) has emerged as an exciting potential strategy for immune system modulation. Both EPO-receptor structure and its presence on leukocytes indicated that beyond erythropoietic function, suggesting that EPO might possess some immunomodulatory properties.