Safety and Homing of Human Dental Pulp Stromal Cells in Head and Neck Cancer

Abstract

Background: Head and neck cancer (HNC) is one of the most common cancers, associated with a huge mortality and morbidity. In order to improve patient outcomes, more e cient and targeted therapies are essential. Bone marrow-derived mesenchymal stromal cells (BM-MSCs) express tumour homing capacity, which could be exploited to target anti-cancer drug delivery to the tumour region and reduce adverse sideeffects. Nevertheless, dental pulp stromal cells (DPSCs), an MSC-like population present in teeth, could offer important clinical bene ts because of their easy isolation and superior proliferation compared to BM-MSCs. Therefore, we aimed to elucidate the tumour homing and safe usage of DPSCs to treat HNC. Methods: The in vivo survival as well as the effect of intratumourally administered DPSCs on tumour aggressiveness was tested in a HNC xenograft mouse model by using bioluminescence imaging (BLI), (immuno)histology and qRT-PCR. Furthermore, the in vitro and in vivo tumour homing capacity of DPSCs towards a HNC cell line were evaluated by a transwell migration assay and BLI, respectively.Results: Intratumourally injected DPSCs survived for at least two weeks in the tumour micro-environment and had no signi cant in uence on tumour morphology, growth, angiogenesis and epithelial-tomesenchymal transition. In addition, DPSCs migrated towards tumour cells in vitro, which could not be con rmed after their in vivo intravenous, intraperitoneal or peritumoural injection under the tested experimental conditions.Conclusions: Our research suggests that intratumourally delivered DPSCs might be used as safe factories for the continuous delivery of anti-cancer drugs in HNC. Nevertheless, further optimization as well as e cacy studies are necessary to understand and improve in vivo tumour homing and determine the optimal experimental set-up of stem cell-based cancer therapies, including dosing and timing.

Potent antitumor efficacy of human dental pulp stem cells armed with YSCH-01 oncolytic adenovirus

“…It has been previously reported that hDPSCs exhibit significant migration towards tumor cells in in vitro assays. However, the tumor tropism of hDPSCs could not be confirmed in vivo following intravenous, intraperitoneal, or peritumoral injection under the tested experimental conditions [ 16 ]. In contrast, our results confirmed the tumor tropism of hDPSCs and demonstrated the anti-cancer efficacy of YSCH-01/hDPSC in vivo.…”

“…Among the most well-known signaling pathway is the CXCR4/SDF-1α axis [ 15 ]. However, a study investigating subcutaneous, intravenous, and peritumoral injection of hDPSCs into subcutaneous tongue cancer models revealed no evidence of stem cell presence in the tumor tissue [ 16 ]. This observation suggests that hDPSCs may not effectively migrate into tumors.…”

Clinical trials using dental stem cells: 2022 update

“…Similar to the regeneration of damaged tissue, tumors exert chemotactic effects on MSCs, affecting their recruitment to tumor sites[ 75 - 77 ]. Current studies have shown that MSCs have bidirectional, anti-cancer and pro-cancer, regulatory effects, which raises safety concerns for clinical application.…”

Therapeutic potential of dental pulp stem cells and their derivatives: Insights from basic research toward clinical applications

“…In the treatment of these diseases using DPSCs, injection is one of the more commonly used forms. Stem cell injections are the easiest cell therapy products to prepare, and the commonly used vehicles at present for resuspension of stem cells is phosphate-buffered saline[ 69 - 73 ], Hank's Balanced Salt Solution[ 15 ], normal saline[ 14 , 67 , 74 - 76 ], and modified medium[ 66 , 68 , 77 - 79 ]. These mediators have no therapeutic effect and only serve as transport vectors for stem cells, so it is possible to observe the monotherapy effect of transplanted stem cells and rule out the influence of carriers.…”