RT info:eu-repo/semantics/article
T1 Retinal neuroprotective effect of mesenchymal stem cells secretome through modulation of oxidative stress, autophagy, and programmed cell death
A1 Usategui Martín, Ricardo
A1 Puertas Neyra, Kevin Louis
A1 Galindo Cabello, Nadia Regina
A1 Hernández Rodríguez, Leticia A
A1 González Pérez, Fernando
A1 Rodríguez Cabello, José Carlos
A1 González Sarmiento, Rogelio
A1 Pastor Jimeno, José Carlos
A1 Fernández Bueno, Iván
K1 Mesenchymal stem cells secretome
K1 Retinal neuroprotective effect
K1 Retinal
K1 32 Ciencias Médicas
K1 33 Ciencias Tecnológicas
AB Purpose: Degenerative mechanisms of retinal neurodegenerative diseases (RND) share common cellular and molecular signalization pathways. Curative treatment does not exist and cell-based therapy, through the paracrine properties of mesenchymal stem cells (MSC), is a potential unspecific treatment for RND. This study aimed to evaluate the neuroprotective capability of human bone marrow (bm) MSC secretome and its potential to modulate retinal responses to neurodegeneration.Methods: An in vitro model of spontaneous retinal neurodegeneration was used to compare three days of monocultured neuroretina (NR), NR cocultured with bmMSC, and NR cultured with bmMSC secretome. We evaluated retinal morphology markers (Lectin peanut agglutinin, rhodopsin, protein kinase C α isoform, neuronal-specific nuclear protein, glial fibrillary acidic protein, TdT-mediated dUTP nick-end labeling, and vimentin) and proteins involved in apoptosis (apoptosis-inductor factor, caspase-3), necroptosis (MLKL), and autophagy (p62). Besides, we analyzed the relative mRNA expression through qPCR of genes involved in apoptosis (BAX, BCL2, CASP3, CASP8, CASP9), necroptosis (MLKL, RIPK1, RIPK3), autophagy (ATG7, BCLIN1, LC3B, mTOR, SQSTM1), oxidative stress (COX2, CYBA, CYBB, GPX6, SOD1, TXN2, TXNRD1) and inflammation (IL1, IL6, IL10, TGFb1, TNFa).Results: The bmMSC secretome preserves retinal morphology, limits pro-apoptotic– and pro-necroptotic–related gene and protein expression, modulates autophagy-related genes and proteins, and stimulates the activation of antioxidant-associated genes.Conclusions: The neuroprotective ability of the bmMSC secretome is associated with activation of antioxidant machinery, modulation of autophagy, and inhibition of apoptosis and necroptosis during retinal degeneration. The neuroprotective effect of bmMSC secretomes in the presence/absence of MSC looks similar. Our current results reinforce the hypothesis that the human bmMSC secretome slows retinal neurodegeneration and may be a therapeutic option for treating RND.
PB Association for Research in Vision and Ophthalmology
SN 1552-5783
YR 2022
FD 2022
LK https://uvadoc.uva.es/handle/10324/54103
UL https://uvadoc.uva.es/handle/10324/54103
LA eng
NO Investigative Opthalmology & Visual Science, 2022, vol. 63, n. 4, p. 27
NO Producción Científica
DS UVaDOC
RD 11-jul-2024