Encapsulated Mesenchymal Stem Cells for Central Nervous System Repair

Mesenchymal stromal cells (MSC) have long been regarded as a cell source with the potential to provide therapies for various different tissue pathologies. They were originally identified for their ability to adhere to tissue culture plastic and gained favor due to their tremendous ability to propagate[1]. It was this finding as well as their ability to differentiate into lineages of mesoderm which have long made MSC a potential tool for autologous cellular replacement therapies [2, 3]. More recently, their cyto-protective role has been realized and been implicated in the benefit achieved in treating various different tissue pathologies. MSC have been found to secrete several different cytokines and growth factors in vitro. Furthermore, these factors can be modulated based on the environment MSC are exposed to. MSC have shown therapeutic benefits in models of GVHD, myocardial infarction, fulminant hepatic failure, central nervous system trauma and others, without any apparent cellular replacement. These advances propelled MSC to the fore front of potential cellular therapies and many are seeking to take advantage of their tissue protective properties. However, several draw backs in current methods of MSC implantation limit the ability to carry out safe and controlled clinical trials. Limitation with current MSC implantation approaches include; 1) directly transplanted MSCs exposed to the complex injury environment may be affected themselves early in the treatment processes, 2) MSC may also migrate to undesired tissue locations and 3) may differentiate into undesired end stage cells. These issues severally limit the translatability of MSC treatments in clinical settings; they make controlling experiments very difficult. There becomes a need to develop engineered methods for delivering these cells in a controlled manner. In order to circumvent these potential problems, we propose to use an alginate microencapsulation system as a vehicle for MSC delivery taking advantage of the soluble factors MSC provide.