Identification and characterization of a new source of adult human neural progenitors

Jinan Behnan,Jinan Behnan,Gaetano Finocchiaro,Biljana Stangeland,Wayne Murrell,Biljana Stangeland,Giovanni Tringali,Torstein R Meling,Tiziana Langella

doi:10.1038/cddis.2017.368

Abstract

Adult neural progenitor cells (aNPCs) are a potential source for cell based therapy for neurodegenerative diseases and traumatic brain injuries. These cells have been traditionally isolated from hippocampus, subventricular zone and white matter. However, there is still a need for an easily accessible source with better yield to counter the limitations of small surgical samples of previously characterized aNPCs. Here we show that ultrasonic aspirate (UA) samples currently considered as ‘biological waste after surgery,' offer a good source for aNPCs. Furthermore, we show that culture conditions dictated the phenotype of cells across patients. The neurosphere-enriched cells were more similar to freshly isolated brain cells, while cells expanded adherently in serum conditions were similar to mesenchymal stem cells. However, cells expanded in these adherent conditions expressed some NPC and glial markers in addition to active canonical Wnt signaling. This suggests a mesenchymal-neuroectodermal hybrid nature of these cells. Finally, we show that UA-NPCs are comparable to those from neurogenic regions. Our findings suggest that UA samples can be used as a source for fresh and in vitro propagated aNPCs that could have various clinical applications.

Highlights

An increased interest in the potential for therapeutic use of adult neural stem cells (NSCs) or neural progenitor cells (NPCs) has pushed forward efforts to find reliable sources for isolating these cells and optimizing protocols for expanding them ex-vivo
Lojewski et al compared NPCs from white matter (WM) to those derived from HPC and showed that the fresh primary cells isolated from tissue of both compartments express oligodendrocyte progenitor markers: A2B5, oligodendrocyte transcription factor 2 (OLIG2), neuron-glial antigen 2 (NG2), but not Nestin, SOX2 or CD133 which are known as NSC markers
We show that Ultrasonic aspirate (UA)-NPCs enriched under sphere conditions express comparable stemness markers to those obtained from neurogenic regions: subventricular zone (SVZ) and HPC

Summary

Introduction

An increased interest in the potential for therapeutic use of adult neural stem cells (NSCs) or neural progenitor cells (NPCs) has pushed forward efforts to find reliable sources for isolating these cells and optimizing protocols for expanding them ex-vivo. Neurosphere cultures established from these two compartments, WM and HPC, showed that cultured cells did express SOX2 and Nestin, but not CD133 and present very similar transcriptome profiles.[9] Another study was able to detect the expression of SOX2 in white matter tissue (~2%) and showed that these cells are more like glial progenitors.[10]. Protein expression together with multilineage neural and mesenchymal differentiation showed that both adherent serum cultures AD1 and AD10 resemble MSCs. The molecular profiling showed that cells isolated from fresh samples are clearly different from cells cultured in all three conditions. We show that UA-NPCs enriched under sphere conditions express comparable stemness markers to those obtained from neurogenic regions: SVZ and HPC

Methods

Results

Conclusion