The dual effect of mesenchymal stem cells on tumour growth and tumour angiogenesis

Abstract

IntroductionUnderstanding the multiple biological functions played by human mesenchymal stem cells (hMSCs) as well as their development as therapeutics in regenerative medicine or in cancer treatment are major fields of research. Indeed, it has been established that hMSCs play a central role in the pathogenesis and progression of tumours, but their impact on tumour growth remains controversial.MethodsIn this study, we investigated the influence of hMSCs on the growth of pre-established tumours. We engrafted nude mice with luciferase-positive mouse adenocarcinoma cells (TSA-Luc+) to obtain subcutaneous or lung tumours. When tumour presence was confirmed by non-invasive bioluminescence imaging, hMSCs were injected into the periphery of the SC tumours or delivered by systemic intravenous injection in mice bearing either SC tumours or lung metastasis.ResultsRegardless of the tumour model and mode of hMSC injection, hMSC administration was always associated with decreased tumour growth due to an inhibition of tumour cell proliferation, likely resulting from deep modifications of the tumour angiogenesis. Indeed, we established that although hMSCs can induce the formation of new blood vessels in a non-tumoural cellulose sponge model in mice, they do not modify the overall amount of haemoglobin delivered into the SC tumours or lung metastasis. We observed that these tumour vessels were reduced in number but were longer.ConclusionsOur results suggest that hMSCs injection decreased solid tumour growth in mice and modified tumour vasculature, which confirms hMSCs could be interesting to use for the treatment of pre-established tumours.

Mesenchymal Stem Cells: How Can we Realize their Therapeutic Potential in Cancer Therapy?

“…For example, Kaposi sarcoma tumours in mice were growth inhibited by around two thirds via inactivation of Akt-mediated pathways in the presence of MSCs [28] and murine hepatoma and lymphoma cell line growth was reduced by up to 90% in vitro and in vivo [29]. Similar results were found using lung cancer cell line A549 and metastasis was also inhibited [30,31]. MSCs have also been shown to decrease breast cancer cell migration and invasion via production of the tissue inhibitors of matrix metalloproteinases TIMP-1 [32] and TIMP-2 [33].…”

Molecular imaging for assessment of mesenchymal stem cells mediated breast cancer therapy

“…The origins of MSCs should be taken into account when deciding the antitumor effect, as did in the case of hUC-MSCs which inhibit glioblastoma proliferation, but adipose tissue-derived not [26]. Considered the antitumor effect, human MSCs could be more interesting to use for the treatment of pre-established tumors [27]. We speculated that different tissue origin of MSCs, delivery methods, individual variations are key points for future MSCs mediated cancer therapy [25].…”

Prostate tumor-induced angiogenesis is blocked by exosomes derived from menstrual stem cells through the inhibition of reactive oxygen species

“…Mesenchymal stem cells (MSCs) are multipotent cells that exhibit a marked tropism for tumors [7, 8] and display controversial angiogenic properties: while some reports showed that MSCs support tumor angiogenesis [9–11], other studies observed a range of anti-angiogenic properties [12–14]. This can be explained by many reasons, such as the complexity of the different MSCs origins and their specific properties on different cancer cell types [15–17], as a consequence of the specific crosstalk between tumor cells, tumor microenvironment and MSCs, and by the MSCs-derived factors produced within the tumor [18].…”