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

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Stem Cells: Biology and Engineering

Part of the book series: Advances in Experimental Medicine and Biology ((ICRRM,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.

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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

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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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Authors and Affiliations

  1. Institute for Cellular and Molecular Medicine, Department of Immunology, and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

    Ahmed Kolade Oloyo, Melvin Anyasi Ambele & Michael Sean Pepper

  2. Department of Physiology, Faculty of Basic Medical Science, College of Medicine, University of Lagos, Lagos, Nigeria

    Ahmed Kolade Oloyo

  3. Department of Oral Pathology and Oral Biology, School of Dentistry, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

    Melvin Anyasi Ambele

Authors
  1. Ahmed Kolade Oloyo
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  2. Melvin Anyasi Ambele
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  3. Michael Sean Pepper
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Corresponding author

Correspondence to Michael Sean Pepper .

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Editors and Affiliations

  1. Laboratory of Stem Cell Research and Application, University of Science, Vietnam National University, Ho Chi Minh City, Vietnam

    Phuc Van Pham

Supplementary Tables

Supplementary Tables

Table S1a In vitro experiments that reported a stimulatory effect of BM-MSCs on breast cancer cells
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Table S1b In vivo experiments that reported a stimulatory effect of BM-MSCs on breast cancer cells
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Table S2a In vitro experiments reporting an inhibitory effect of BM-MSCs on breast cancer cells
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Table S2b In vivo experiments reporting an inhibitory effect of BM-MSCs on breast cancer cells
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Table S3a In vitro experiments reporting a stimulatory effect of UC-MSCs on tumour growth
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Table S3b In vivo experiments reporting a stimulatory effect of UC-MSCs on tumour growth
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Table S4a In vitro experiments reporting an inhibitory effect of UC-MSCs on tumour growth
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Table S4b In vivo experiments reporting an inhibitory effect of UC-MSCs on tumour growth
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Table S5a In vitro experiments reporting a stimulatory effect of AD-MSC on tumour growth
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Table S5b In vivo experiments reporting a stimulatory effect of AD-MSC on tumour growth
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Table S6a In vitro experiments reporting an inhibitory effect of AD-MSCs on tumour growth
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Table S6b In vivo experiments reporting an inhibitory effect of AD-MSCs on tumour growth
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Oloyo, A.K., Ambele, M.A., Pepper, M.S. (2017). Contrasting Views on the Role of Mesenchymal Stromal/Stem Cells in Tumour Growth: A Systematic Review of Experimental Design. In: Van Pham, P. (eds) Stem Cells: Biology and Engineering. Advances in Experimental Medicine and Biology(), vol 1083. Springer, Cham. https://doi.org/10.1007/5584_2017_118

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