ALS: All Lies in Stem, Differentiating Stem Cells into Astrocytes and Targeting TDP-43 Protein Plaques in vivo

par Li Shu Yin Han, Emanuel Louis, Christina-Maria Maalouf, Wendy Yang

Année préparatoire de médecine, Université de Montréal

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting 2 per 100,000 annually in the US, making it the most common motor neuron disease [1]. A prion-like mechanism underlies this ailment, involving oxidation and structural damage of the 43-kDA TAR DNA-binding protein (TDP-43), which accumulates as protein aggregates in astrocytes [2]. Consequently, astrocytes in ALS lose neuroprotective property and acquire toxic phenotypes [3]. Stem cells have been shown to reduce amyloid plaques in prion diseases [4]. We will assess its regenerative abilities to halt the disease progression by replacing the diseased astrocytes with in vitro differentiated stem cells and examine the possibility of eliminating TDP-43 aggregates with stem cells. Therapeutic astrocytes will be differentiated in vitro from bone marrow-derived mesenchymal stem cells that are bromodeoxyuridine-labelled and then transplanted into ventral horns of ALS mice models [5]. Their brains will be harvested and sectioned, then prepared with paraformaldehyde for immunohistochemistry. Astrocyte in vivo migration will be monitored by the presence of the rabbit-sourced glial fibrillary acidic protein GFAP marker on motor neurons [6]. The elimination of TDP-43 plaques will be visualized by using fluorescent-labeled, rabbit-sourced anti-TDP-43 antibodies. We expect a reduction of labelled TDP-43 in mice neurological samples, indicating the corresponding reduction of protein aggregates, as suggested by the previous analysis of affected homogenate using immunofluorescence [4]. These findings seek to show that stem cells constitute a possible future avenue for the treatment of ALS, which may save the lives of many patients living through this debilitating disease and alleviate the disease burden worldwide.

Key words : ALS, immunohistochemistry, TDP-43, astrocytes, stem cell

Références

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