Identification of two distinct mesenchymal stromal cell populations in human malignant glioma

Andreas Svensson,Johan Bengzon,Sofia Eberstål,Stefan Scheding,Tania Ramos-Moreno

doi:10.1007/s11060-016-2302-y

Andreas Svensson, Johan Bengzon + Show 3 more

Open Access

https://doi.org/10.1007/s11060-016-2302-y

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Abstract

Gene profiling has revealed that malignant gliomas can be divided into four distinct molecular subtypes, where tumors with a mesenchymal gene expression are correlated with short survival. The present investigation was undertaken to clarify whether human malignant gliomas contain endogenous mesenchymal stromal cells (MSC), fulfilling consensus criteria defined by The International Society for Cellular Therapy, recruited from the host. We found that MSC-like cells can be isolated from primary human malignant gliomas. Two distinct MSC-like cell populations, differing in their expression of the CD90 surface marker, were discovered after cell sorting. RNA sequencing revealed further genetic differences between these two cell populations and MSC-like cells lacking CD90 produced higher amounts of VEGF and PGE2 compared to cells with the true MSC phenotype, implying that the CD90− MSC-like cells most probably are more active in tumor vascularization and immunosuppression than their CD90+ counterpart. The results highlight the CD90− subpopulation as an important tumor component, however, its functional effects in glioma remains to be resolved. Using the protocols presented here, it will be possible to isolate, characterize and analyze brain tumor-derived MSC-like cells in more detail and to further test their functions in vitro and in in vivo xenograft models of glioma.

Highlights

Mesenchymal stromal cells (MSC) are found in a variety of tissues where they constitute a stem cell pool [1]
Human MSCs are defined according to in vitro consensus criteria developed by The International Society for Cellular Therapy (ISCT); in culture, MSC should adhere to plastic, they should express CD73, CD90, CD105 but lack expression of CD11b or CD14, CD19 or CD79α, CD34, CD45 and HLA-DR, and they should be able to differentiate into adipocytes, osteoblasts and chondrocytes [7]
Another interesting finding was that the low-grade astrocytoma (AC45) contained notably fewer MSC-like cells than most of the high-grade GBMs, no correlation was observed between patient survival and the % of MSC-like cells in the tumor

Summary

Introduction

Mesenchymal stromal cells (MSC) are found in a variety of tissues where they constitute a stem cell pool [1]. They can be mobilized to sites of inflammation and angiogenesis, such as wounded tissue and, importantly, various solid cancers [2,3,4]. MSC constitute a promising vector system for cell mediated gene therapy [8] as they display inherent tumor-tropic migratory capabilities [9, 10] are found in several adult tissues [1] and are easy to isolate and expand in vitro [11].

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