The Potential of Mesenchymal Stem Cell in Prion Research

Abstract

Scrapie and bovine spongiform encephalopathy are fatal neurodegenerative diseases caused by the accumulation of a misfolded protein (PrP(res)), the pathological form of the cellular prion protein (PrP(C)). For the last decades, prion research has greatly progressed, but many questions need to be solved about prion replication mechanisms, cell toxicity, differences in genetic susceptibility, species barrier or the nature of prion strains. These studies can be developed in murine models of transmissible spongiform encephalopathies, although development of cell models for prion replication and sample titration could reduce economic and timing costs and also serve for basic research and treatment testing. Some murine cell lines can replicate scrapie strains previously adapted in mice and very few show the toxic effects of prion accumulation. Brain cell primary cultures can be more accurate models but are difficult to develop in naturally susceptible species like humans or domestic ruminants. Stem cells can be differentiated into neuron-like cells and be infected by prions. However, the use of embryo stem cells causes ethical problems in humans. Mesenchymal stem cells (MSCs) can be isolated from many adult tissues, including bone marrow, adipose tissue or even peripheral blood. These cells differentiate into neuronal cells, express PrP(C) and can be infected by prions in vitro. In addition, in the last years, these cells are being used to develop therapies for many diseases, including neurodegenerative diseases. We review here the use of cell models in prion research with a special interest in the potential use of MSCs.

Cellular and Molecular Mechanisms Mediated by recPrPC Involved in the Neuronal Differentiation Process of Mesenchymal Stem Cells

“…In a previous work, we used human dental pulp stem cell (hDPSCs) as the experimental model to develop an in vitro system used to study proliferation and differentiation process [22]. hDPSCs represent a kind of adult mesenchymal stem cells that show the ability to differentiate in vitro in several multilineages such as odontoblasts, osteoblasts, chondrocytes, adipocytes and neurons [23,24,25,26,27,28,29,30].…”

“…hDPSCs represent a kind of adult mesenchymal stem cells that show the ability to differentiate in vitro in several multilineages such as odontoblasts, osteoblasts, chondrocytes, adipocytes and neurons [23,24,25,26,27,28,29,30]. The fact that hDPSCs can express basally PrP C [21] and show the ability to differentiate into neuronal-like cells [31] or dopaminergic neuron-like cells [32], prompt it to be considered as a cellular model for the study of neurodegenerative diseases, such as Alzheimer, Parkinson and Huntington diseases [22,33,34].…”

Role of Prion protein-EGFR multimolecular complex during neuronal differentiation of human dental pulp-derived stem cells

“…In particular, hDPSCs show the ability to differentiate into neuronallike cells [13] or dopaminergic neuron-like cells [14]. It makes them as a cellular model candidate for the study and treatment of neurodegenerative diseases, such as Alzheimer, Parkinson and Huntington disease [15][16][17].…”

“…The expression of PrP C makes mesenchymal stem cells good candidates to develop in vitro system for the study of prion infectivity and multiplication [15].…”

Regenerative Potential of DPSCs and Revascularization: Direct, Paracrine or Autocrine Effect?

“…This conditional media from DPSCs can enhance the growth rate of Schwann cells and induce neurite outgrowth in vitro [29,31]. It makes them a cellular model candidate for the study and treatment of neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's disease [32,33].…”