Author(s): Coutinho, Maria Francisca ; Santos, Juliana Inês ; Matos, Liliana ; Teles, Elisa Leão ; Martins, Esmeralda ; Matos, Paula Garcia ; Janeiro, Patrícia ; Marques, Raquel ; Silva, António ; Prata, Maria João ; Alves, Sandra
Date: 2021
Persistent ID: http://hdl.handle.net/10400.18/8145
Origin: Repositório Científico do Instituto Nacional de Saúde
Subject(s): Lysosomal Storage Disorders; Doenças Lisossomais de sobrecarga; Doenças Genéticas; Genética Humana
Lysosomal storage disorders (LSD) are a group of rare diseases caused mutations in genes that encode lysosomal enzymes, membrane proteins or transporters. This leads to an accumulation of undegraded substrates, which ultimately causes a broad range of highly debilitating clinical symptoms affecting multiple organs/systems, including the central nervous system. Yet, most therapies for LSD are limited to treating non-neurological signs. Thus, there is an urgent need for the development of new ones that can tackle the neuronal pathogenesis. Fortunately, the portfolio of innovative therapeutic approaches under development has been growing tremendously and the need for proper models grows alongside. To address this concern, we propose the development and characterization of innovative patient-derived cell models for early onset neurodegenerative LSD using dental pulp stem cells (DPSC) from deciduous “baby” teeth. DPSCs hold potential to give rise to a variety of cells including functionally active neurons. Nevertheless, to the best of our knowledge, this sort of technology hasn’t yet been applied to samples obtained from LSD patients. This will be a total innovation in the field and we believe it holds potential to set a new trend for investigating LSD as it relies on a non-invasive, cost effective approach that can be set as a routine in any lab with standard cell culture conditions. Here we present an update on this project, summarizing its rationale and current results, while giving an overview of the whole protocol and discussing its potential applications. Briefly, over the last months, we have successfully implemented the protocol for the establishment of control DPSC cultures in our lab and are currently working on the differentiation protocol, which will allow the formation of mixed neuronal and glial cultures. We are also actively working with patients’ associations and a team of expert pediatricians from the major reference centers for treatment of LSD to identify potential volunteers for baby teeth collection, having already approached several families, who are now actively involved in the project and willing to send us deciduous baby teeth, as soon as they fall. Acknowledgments This work is partially supported by the Portuguese Society for Metabolic Disorders (SPDM - Bolsa SPDM de apoio à investigação Dr. Aguinaldo Cabral 2018; 2019DGH1629/SPDM2018I&D) and Sanfilippo Children's Foundation (2019DGH1656/SCF2019I&D).
