Dental pulp stem cells used to deliver the anticancer drug paclitaxel

Hamideh Salehi (1) , Siham Al-Arag (1) , Elodie Middendorp (1) , Csilla Gergely (2) , Frederic J. G. Cuisinier (1, 3) , Valérie Orti (1)

1 LBN - Laboratoire de Bioingénierie et NanoSciences
2 L2C - Laboratoire Charles Coulomb
3 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]

Background: Understanding stem cell behavior as a delivery tool in cancer therapy is essential for evaluating their future clinical potential. Previous in-vivo studies proved the use of mesenchymal stem cells (MSCs) for local delivery of the commonest anticancer drug, paclitaxel (PTX). Dental pulp is a relatively abundant noninvasive source of MSCs. We assess dental pulp stem cells (DPSCs), for the first time, as anticancer drug carriers. Confocal Raman microscopy is a unique tool to trace drug and cell viability without labeling. Methods: Drug uptake and cell apoptosis are identified through confocal Raman microscope. We traced translocation of cytochrome c enzyme from the mitochondria, as a biomarker for apoptosis, after testing both cancer and stem cells. The viability of stem cells was checked by means of confocal Raman microscope and by cytotoxicity assays. Results: In this study, we prove that DPSCs can be loaded in vitro with the anticancerous drug without affecting their viability, which is later released in the culture medium of breast cancer cells (MCF-7 cells) in a time-dependent fashion. The induced cytotoxic damage in MCF-7 cells was observed consequently after PTX release by DPSCs. Additionally, quantitative Raman images of intracellular drug uptake in DPSCs and MCF-7 cells were obtained. Cytotoxic assays prove the DPSCs to be more resistant to PTX as compared to bone marrow-derived MSCs, provided similar conditions. Conclusions: Applications of dental stem cells for targeted treatment of cancer could be a revolution to reduce morbidity due to chemotherapy, and to increase the efficacy of systemic cancer treatment.

Mots clés: Raman spectroscopy; Dental pulp stem cells; Cancer; Paclitaxel; Apoptosis

Domaines: Biotechnologies; Sciences pharmaceutiques

Hamideh Salehi, Siham Al-Arag, Elodie Middendorp, Csilla Gergely, Frederic J. G. Cuisinier, et al.. Dental pulp stem cells used to deliver the anticancer drug paclitaxel. Stem Cell Research and Therapy, 2018, 9, pp.103. ⟨10.1186/s13287-018-0831-3⟩. ⟨hal-01775198⟩