Mesenchymal stem cells for treatment of CNS injury

Abstract

Brain and spinal cord injuries present significant therapeutic challenges. The treatments available for these conditions are largely ineffective, partly due to limitations in directly targeting the therapeutic agents to sites of pathology within the central nervous system (CNS). The use of stem cells to treat these conditions presents a novel therapeutic strategy. A variety of stem cell treatments have been examined in animal models of CNS trauma. Many of these studies have used stem cells as a cell-replacement strategy. These investigations have also highlighted the significant limitations of this approach. Another potential strategy for stem cell therapy utilises stem cells as a delivery mechanism for therapeutic molecules. This review surveys the literature relevant to the potential of mesenchymal stem cells for delivery of therapeutic agents in CNS trauma in humans.

Keywords: Mesenchymal Stem Cell; Spinal Cord Injury; Traumatic Brain Injury..

Fig. (1)

Prevention of oligodendrocyte apoptosis by MSCs. MSC transplantation can reduce apoptosis of oligodendrocytes following CNS injury through secretion of survival factors such as IGF. This results in reduction of demyelination of intact axons as part of the secondary injury mechanisms in which oligodendrocytes retract their processes and then become atrophied and undergo apoptosis. The denuded axons subsequently degenerate and develop axonal swellings in which the tubulin network depolymerises.

Fig. (2)

Therapeutic potential of MSCs in CNS trauma. (A) MSCs have several properties that can be harnessed for regenerative medical approaches such as their ability to suppress the immune system and secrete growth factors, and their capacity for being used as cellular vectors for therapeutic molecules such as peptides that inhibit myelin derived inhibitory factors (MAIFs) that prevent axonal regeneration. (B) Transplantation of MSCs, particularly ones that are genetically manipulated to secrete neurotrophic factors such as BDNF, can result in regeneration of injured axons and their extension into the lesion site, and reduction of the size of the spinal cord lesion.

Fig. (3)

MSCs have the capacity to modulate the immune response by reducing pro-inflammatory immune cell function and the production of inflammatory cytokines whilst promoting regulatory T cell proliferation and secretion of IL-4 and IL-10.