The role of human postnatal bone marrow-derived mesenchymal stem cells and their importance in growth, spinal cord injury and other neurodegenerative disorders

Abstract

Mesenchymal stem cells (MSCs) are pluripotent cells that differentiate into cells of mesodermal origin and transdifferentiate into ectodermal and endodermal cell types. Physiologically, MSCs are primarily responsible for the regeneration and growth of cells and tissues derived from a mesodermal lineage; MSCs form bone, cartilage, muscle, and connective tissue. MSCs can also transdifferentiate with high efficiency to functional neurons: microglia and oligodendrocytes. MSCs respond to environmental cues such as cytokines and these cues affect their development and fate. Since cytokines and other inflammatory mediators are also expected at sites of spinal cord injury (SCI), simple implantation of MSCs and/or their differentiated cells for therapeutic benefits might be premature unless the basic science precedes translational science. This is particularly valid as each individual has a unique immune response. A similar argument could be made for embryonic stem cells (ESCs). However, the unstable behavior of ESC to form tumors, as well as rapid generation of mixed cell types, makes MSCs a more desirable stem cell for translational science. This chapter briefly explains the role of MSCs in normal growth and development before discussing approaches by whichMSCs can be applied to SCI repair and other neurodegenerative disorders. The mechanism by which microenvironmental factors can affect stem cell development, growth, and therapies is also discussed. In addition to the potential of direct application of stem cells or their differentiated cells, MSCs can be used as models to understand axonal repair, which could lead to the development of new drugs for SCI. These models could test novel factors to repair neurons. Any identified factor could be delivered directly or by gene therapy. Co-culture methods employing MSCs are significant to long-term investigation for rapid screening of compounds, with simultaneous understanding of repair mechanisms of axotomized neurons. The model could be translated in parallel with other stem cell therapies for SCI repair.