Dr. Javier Sierra Istúriz   j.sierra.prof@ufv.es

RESEARCH LINE
Olfactory ensheathing glia: cellular reprogramming and regeneration of central nervous system lesions.

One of the unsolved problems of molecular and cellular biology is to modify the poor regenerative capacity of neurons in the central nervous system (CNS). Recent studies have found that olfactory ensheathing glia (OEG) cells can act as a mediator of regeneration in the CNS. Likewise, reprogramming of non-neuronal cell types (fibroblasts or astrocytes) to functional neurons, after genetic modification, has been achieved; in these studies, recovery of the injured region after transplantation of the induced neurons (iNs) is observed.

In our laboratory,two lines of work are followed:

1. The identification of those molecules and signaling pathways expressed by GEO that are relevant for adult axonal regeneration, with the aim of finding potential therapeutic targets for the pharmacological control of CNS regeneration. We are currently working with the Wnt/βcatenin signaling pathway.
2. The reprogramming of primary cultures of human and adult rat GEO to neurons. For this purpose, different neurogenic transcription factors are overexpressed in GEO cells by transduction with a lentivector. Another approach is the activation or inhibition of signaling pathways through the use of drugs (“small molecules”)

Cell therapy for spinal cord injury with olfactory ensheathing glia cells (OECs). Gómez RM, Sánchez MY, Portela-Lomba M, Ghotme K, Barreto GE, Sierra J, Moreno-Flores MT. Glia. (2018) 66(7):1267-1301. doi: 10.1002/glia.23282.

Olfactory Ensheathing Cell-Conditioned Medium Reverts Aβ25-35-Induced Oxidative Damage in SH-SY5Y Cells by Modulating the Mitochondria-Mediated Apoptotic Pathway. Fu QQ, Wei L, Sierra J, Cheng JZ, Moreno-Flores MT, You H, Yu HR. Cell Mol Neurobiol. (2017) 37(6):1043-1054.

Transduction of an immortalized olfactory ensheathing glia cell line with the green fluorescent protein (GFP) gene: Evaluation of its neuroregenerative capacity as a proof of concept. Plaza N, Simón D, Sierra J, Moreno-Flores MT. Neurosci Lett. (2016) 612:25-31.

Coculture of Axotomized Rat Retinal Ganglion Neurons with Olfactory Ensheathing Glia, as an In Vitro Model of Adult Axonal Regeneration. Portela-Lomba M, Simón D, Russo C, Sierra J, Moreno-Flores MT. J Vis Exp. 2020 Nov 2;(165). doi: 10.3791/61863. PMID: 33191937.

Title: Transdifferentiation of human enveloped glia and identification of novel therapeutic targets for spinal cord regeneration. SAF2017-82736-C2-1-R

Funding entity: State Programme for Research, Development and Innovation Oriented to Society’s Challenges 2017. MINECO.

Duration: January 2018-December 2020 // Amount: 72,358€.

Title: Reprogramming of human enveloped glia.

Funding entity: Universidad Francisco de Vitoria

Duration: 01/2020-12/2020 // Amount: 6000€.

Title: Transdifferentiation of human enveloped glia.

Funding entity: Universidad Francisco de Vitoria

Duration: 01/2019-12/2019 //  Amount: 3500€.

Title: Study of the role of the Wnt pathway in the neuroregenerative capacity of human olfactory ensheathing glia.

Funding entity: UAM-SANTANDER INTER-UNIVERSITY COOPERATION PROJECTS with ASIA (Universidad Autónoma de Madrid).

Duration: 09/2017-02/2019. // Amount: 12,700 €.

Title: Direct reprogramming of adult human enveloped glia.

Funding entity: Universidad Francisco de Vitoria.

Duration: 01/2021-12/2021. //   Amount: 10700€.

Patents

Authors: Mª Teresa Moreno Flores, Mª Jesús Martín Bermejo, Érika Pastrana, Filip Lim, Jesús Ávila, Javier Díaz-Nido, and Francisco Wandosell. Title: Reversible immortalization of OEG from human olfactory bulbs as a tool to promote spinal cord regeneration. Priority number: WO 2004/012513 A1 (UK0316882.0). Country of priority: Great Britain. Date of priority: 18/07/2003 Proprietary: C.B.M.S.O. (C.S.I.C.-U.A.M.), Owner: Noscira. Countries to which it was extended: Australia, Canada, China, United States, Europe, India, Israel, Japan, Mexico and Republic of Korea.