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Contrasting Views on the Role of Mesenchymal Stromal/Stem Cells in Tumour Growth: A Systematic Review of Experimental Design

  • Ahmed Kolade Oloyo
  • Melvin Anyasi Ambele
  • Michael Sean Pepper
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1083)

Abstract

The effect of mesenchymal stromal/stem cells (MSCs) on tumour growth remains controversial. Experimental evidence supports both an inhibitory and a stimulatory effect. We have assessed factors responsible for the contrasting effects of MSCs on tumour growth by doing a meta-analysis of existing literature between 2000 and May 2017. We assessed 183 original research articles comprising 338 experiments. We considered (a) in vivo and in vitro experiments, (b) whether in vivo studies were syngeneic or xenogeneic, and (c) if animals were immune competent or deficient. Furthermore, the sources and types of cancer cells and MSCs were considered together with modes of cancer induction and MSC administration. 56% of all 338 experiments reported that MSCs promote tumour growth. 78% and 79% of all experiments sourced human MSCs and cancer cells, respectively. MSCs were used in their naïve and engineered form in 86% and 14% of experiments, respectively, the latter to produce factors that could alter either their activity or that of the tumour. 53% of all experiments were conducted in vitro with 60% exposing cancer cells to MSCs via coculture. Of all in vivo experiments, 79% were xenogeneic and 63% were conducted in immune-competent animals. Tumour growth was inhibited in 80% of experiments that used umbilical cord-derived MSCs, whereas tumour growth was promoted in 64% and 57% of experiments that used bone marrow- and adipose tissue-derived MSCs, respectively. This contrasting effect of MSCs on tumour growth observed under different experimental conditions may reflect differences in experimental design. This analysis calls for careful consideration of experimental design given the large number of MSC clinical trials currently underway.

Keywords

Cancer Mesenchymal stem cell Syngeneic Tumour Xenogeneic 

Abbreviations

AD

Adipose tissue

BM

Bone marrow

CC

Coculture

CCR2

C-C motif chemokine receptor 2

c-Kit

Tyrosine-protein kinase Kit also known as mast/stem cell growth factor receptor (SCFR)

CM

Conditioned medium

c-Met

Tyrosine-protein kinase Met or hepatocyte growth factor receptor

CXCR4

C-X-C motif chemokine receptor 4

EGF

Epithelial growth factor

HGF

Hepatocyte growth factor

HNSCC

Head and neck squamous cell carcinoma

IL-1β

Interleukin 1-beta

IL-8

Interleukin 8

IP

Intraperitoneal

IV

Intravenous

MCP-1

Monocyte chemotactic protein 1

MSC

Mesenchymal stromal/stem cell

PDGF

Platelet-derived growth factor

SC

Subcutaneous

SCF

Stem cell factor

SCID

Severe combined immunodeficiency

SDF-1

Stromal cell-derived factor 1

TGF-ß

Transforming growth factor-beta

TNF-α

Tumour necrosis factor alpha

UC

Umbilical cord

VEGF

Vascular endothelial growth factor

VEGFR

Vascular endothelial growth factor receptor

Notes

Acknowledgements

This research was funded by the South African Medical Research Council in terms of theSAMRC’s Flagship Award Project SAMRC-RFA-UFSP-01-2013/STEM CELLS, the SAMRCExtramural Stem Cell Research and Therapy Unit, the National Research Foundation ofSouth Africa (grant no. 86942), the National Health Laboratory Services Research Trust (grant no. 94453), the University of Pretoria Research Development Programme (A0Z778), the University of Pretoria Vice Chancellor’s Postdoctoral Fellowship and the Institute for Cellular and Molecular Medicine of the University of Pretoria.

Competing Interests

No conflicts of interest, financial or otherwise, are declared by the authors.

Authors’ Contribution

MSP conceptualized the idea of the review, AKO and MAA did the literature search, AKO and MAA analysed the data, AKO and MAA prepared the manuscript, MSP edited and reviewed the drafted manuscript and AKO, MAA and MSP approved of the final version of the manuscript.

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Ahmed Kolade Oloyo
    • 1
    • 2
  • Melvin Anyasi Ambele
    • 1
    • 3
  • Michael Sean Pepper
    • 1
  1. 1.Institute for Cellular and Molecular Medicine, Department of Immunology, and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health SciencesUniversity of PretoriaPretoriaSouth Africa
  2. 2.Department of Physiology, Faculty of Basic Medical Science, College of MedicineUniversity of LagosLagosNigeria
  3. 3.Department of Oral Pathology and Oral Biology, School of Dentistry, Faculty of Health SciencesUniversity of PretoriaPretoriaSouth Africa

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