Mo1588 - Enteric Glial Cell Plasticity: Astrocytes, Schwann Cell, Neurons and Stem Cells all-in-one

Post-traumatic lesions with transection of the facial nerve present limited functional outcome even after repair by gold-standard microsurgical techniques. Stem cell engraftment combined with surgical repair has been reported as a beneficial alternative. However, the best association between the source of stem cell and the nature of conduit, as well as the long-term postoperative cell viability are still matters of debate. We aimed to assess the functional and morphological effects of stem cells from human exfoliated deciduous teeth (SHED) in polyglycolic acid tube (PGAt) combined with autografting of rat facial nerve on repair after neurotmesis. The mandibular branch of rat facial nerve submitted to neurotmesis was repaired by autograft and PGAt filled with purified basement membrane matrix with or without SHED. Outcome variables were compound muscle action potential (CMAP) and axon morphometric. Animals from the SHED group had mean CMAP amplitudes and mean axonal diameters significantly higher than the control group ( p < 0.001). Mean axonal densities were significantly higher in the control group ( p = 0.004). The engrafted nerve segment resected 6 weeks after surgery presented cells of human origin that were positive for the Schwann cell marker (S100), indicating viability of transplanted SHED and a Schwann cell-like phenotype. We conclude that regeneration of the mandibular branch of the rat facial nerve was improved by SHED within PGAt. The stem cells integrated and remained viable in the neural tissue for 6 weeks since transplantation, and positive labeling for S100 Schwann-cell marker suggests cells initiated in vivo differentiation.

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OMRT-11. The effect of microenvironment on glioblastoma stem cells therapeutic resistance

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab070.035 ◽

2021 ◽

Vol 3 (Supplement_2) ◽

pp. ii9-ii9

Author(s):

Tamara Lah Turnsek ◽

Barbara Breznik ◽

Bernarda Majc ◽

Metka Novak ◽

Andrej Porčnik ◽

...

Keyword(s):

Stem Cells ◽

Epithelial To Mesenchymal Transition ◽

Combined Treatment ◽

Cell Plasticity ◽

Glioblastoma Stem Cells ◽

Mesenchymal Transition ◽

Non Invasive ◽

Differential Gene

Abstract Epithelial-to-mesenchymal transition (EMT) is an essential molecular and cellular process in physiologic processes and invasion of various types of carcinoma and glioblastoma (GBM) cells. EMT is activated and regulated by specific endogenous triggers in complex network of intercellular interactions and signaling pathways. The hallmark of cancer-linked EMT are intermediate states that show notable cell plasticity, characteristic of cancer stem cells (CSCs), including glioblastoma stem cells – GSCs. GSCs resistance to irradiation (IR) and temozolomide (TMZ) chemotherapy is responsible for early relapses, even at distant brain sites. As GSCs are mostly homing to their “niches” as slowly-dividing GSC-subtype, mimicking a proneural-like non- invasive phenotype PN-genotype, we assume that this, by undergoing an EMT-like transition, GSCs are-reprogrammed to an invasive mesenchymal (MES) GBs/GSCs phenotype in a processes, called PMT (1). However, it is not known, if and by which environmental cues within the niche, this transition of GSCs is induced in vivo. In this work, we are presenting the transriptome data obtained when we exposed GSC spheroids to irradiation alone, TMZ alone and to the combined treatment in vitro and compared their differential genetic fingerprints related to EMT/PMT transition to the GSCs PMT transition, when embedded in their natural microenvironment in the GBM organoid model. The differential gene expression upon GSCs therapeutic perturbation (when alone and vs in the tumoroid microenvironment) will reveal the effects of the major candidate genes, associated with micronevironmendt stromal cells and matrix are contributing their observed EMT/PMT transition of GSCs in vivo. •1. Majc, B., Sever, T., Zarić, M, Breznik, B., Turk, B, Lah Turnšek, T. Epithelial- to-mesenchymal transition as the driver of changing carcinoma and glioblastoma microenvironment. DOI: 10.1016/j.bbamcr.2020.118782

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