Chapter 19 - Stem cell-based therapeutic strategy in delaying prion disease

Abstract

The normal soluble cellular prion protein, PrPC, is responsible for many cellular processes in our body. It gets structurally transformed into a misfolded, insoluble protein called PrPSc. This misfolded protein is responsible for a variety of neurodegenerative diseases commonly known as prion disease. The cause of this structural change from the alpha helical-rich structure of PrPC to the beta sheet-rich structure of PrPSc is not known yet. The PrPSc causes prion amyloids to form and aggregate at different parts of the brain, making it spongy in nature. In humans, prion disease is known by many names, including kuru, Gerstmann-Straussler-Scheinker disease, and Creutzfeldt Jakob disease (CJD). In sheep, it is known as scrapie and in cattle, it is mad cow disease or bovine spongiform encephalopathy (BSE). There are many treatment strategies to control prion disease, such as agents that can dissociate the prion amyloids, small molecules that can target the diseased prion and dissociate it, interfering RNAs, antiprion antibodies, and stem cell therapy. Stem cell therapy deals with the different types of differentiated stem cell grafts incorporation in scrapie-induced mice models. Stem cells from different origins such as neural stem cells (NSCs), embryonic stem cells (ESCs), adult stem cells, fetal neural stem cells (fNSCs), mesenchymal stem cells derived from bone marrow, etc., have been used as grafts to repair the damaged neural cells in the brain of prion-induced mice. Many results have been promising in improving the survival of mice, but very few could indicate a complete cure of the disease. Moreover, the time of disease onset and graft injection plays an important role in obtaining effective results. The strains of prion proteins most commonly used for infecting mice are Chandler, Obihiro, or RML, and the grafting is done well before the onset of disease symptoms to improve mice survival. In this chapter, we will discuss the different stem cell therapeutic approaches so far identified in managing prion disease.