Mini-reviewThe future of mesenchymal stem cell-based therapeutic approaches for cancer – From cells to ghosts
Section snippets
MSCs and their potential use in cancer treatment
MSCs were first isolated and characterised by Friedenstein and his colleagues in the 1960–1970s [1]. They are non-haematopoietic cell precursors, initially found in the bone marrow, but actually present in many other tissues [2]. The International Society of Cellular Therapy (ISCT) uses three criteria to define MSCs [3]: Firstly, MSCs can adhere to plastic under standard culture conditions; secondly, MSCs express cell surface markers including CD105, CD73 and CD90 with no expression of
Do MSCs undergo malignant transformation and form tumours?
In the 2000s it was reported that MSCs could undergo spontaneous, malignant transformation and form tumours in vivo, dramatically increasing the risk of therapeutic use of MSCs [50], [51], [52]. However, these initial reports were subsequently retracted as it turned out that the observed tumour formation was the result of cross-contaminations with cancer cells [53], [54]. In detail, the subsequent analyses showed that the MSC cultures were cross-contaminated with a human sarcoma cell line in
MSCs in preclinical studies and clinical trials
Efficient tumour homing properties will be of importance in MSC-based cancer treatments to surmount the limitations of current therapies such as short drug half-lives and insufficient delivery. The use of an MSC-delivered and continuously produced therapeutic agent could help to overcome these hurdles given that sufficient numbers of MSCs are indeed recruited to tumour lesions. Efforts in increasing the tumour tropism by local irradiation or by overexpressing molecules involved in homing of
The fate of MSCs in vivo
In contrast to other diseases [149], for the treatment of cancer it appears necessary for MSCs to engraft in the relevant tissues, i.e. primary cancer, dissemination routes (e.g. lymphatic system) and metastatic lesions [45]. However, currently, it is not entirely clear how exogenously administered MSCs behave in the human body but what we know is summarised in Supplementary Table 2. Multiple studies have demonstrated the presence of MSCs in the lung, immediately after injection [150], [151],
Concluding remarks
MSCs provide a powerful treatment modality for tumours owing to a series of beneficial features. However, there are still remaining issues that should be addressed and optimised such as the choice of vector and/or therapeutic gene, the optimal route of administration, the question whether allogenic cells provide a good and safe source or whether they will be replaced by autologous iMSCs in the future. Furthermore, it might be possible to derive so called NGs or exosomes from MSCs to avoid many
Conflicts of interest
The authors report no conflicts of interest.
Acknowledgements
The authors acknowledge support from Prostate Cancer UK (RIA15-ST2-014) and Pancreatic Cancer UK (2016 RIF Award).
References (167)
- et al.
Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement
Cytotherapy
(2006) - et al.
Human mesenchymal stem cells maintain transgene expression during expansion and differentiation
Mol. Ther.
(2001) - et al.
Radiation increases invasion of gene-modified mesenchymal stem cells into tumors
Int. J. Radiat. Oncol. Biol. Phys.
(2009) - et al.
Mesenchymal stromal cells alone or expressing interferon-beta suppress pancreatic tumors in vivo, an effect countered by anti-inflammatory treatment
Cytotherapy
(2010) - et al.
A prodrug-doped cellular Trojan Horse for the potential treatment of prostate cancer
Biomaterials
(2016) - et al.
Genetically modified mesenchymal stromal cells in cancer therapy
Cytotherapy
(2016) - et al.
Outgrowth of a transformed cell population derived from normal human BM mesenchymal stem cell culture
Cytotherapy
(2005) - et al.
Large-scale analysis reveals acquisition of lineage-specific chromosomal aberrations in human adult stem cells
Cell Stem Cell
(2011) - et al.
Cytogenetic heterogeneity and their serial dynamic changes during acquisition of cytogenetic aberrations in cultured mesenchymal stem cells
Mutat. Res.
(2015) - et al.
Societe Francaise de Greffe de Moelle et Therapie, Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation
Blood
(2010)