A Study on the Effect of Human Dental Pulp Stem Cell Conditioned Medium on Human Oral Squamous Cell Carcinoma Cell Lines

Hanyu, Shintaro; Sakuma, Kei; Tanaka, Akira

doi:10.2485/jhtb.28.281

Cited by 12 publications

(8 citation statements)

References 38 publications

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“…Similar to our results, they did not observe signi cant effects of hDPSC-derived conditioned medium (CM) on in vitro HNSCC proliferation and therapeutic sensitivity, and in vivo tumour growth, despite the increase in tumour VEGF secretion (45). Con icting results on the impact of other MSC subtypes on in vitro and in vivo HNC cell proliferation, survival, migration, invasion and therapeutic sensitivity have previously been described (46)(47)(48)(49)(50)(51)(52)(53).…”

Section: Discussionsupporting

confidence: 90%

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

Merckx

Monaco

Lambrichts

et al. 2021

Stem Cell Rev and Rep

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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.

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Section: Discussionsupporting

confidence: 90%

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

Merckx

Monaco

Lambrichts

et al. 2021

Stem Cell Rev and Rep

View full text Add to dashboard Cite

show abstract

“…Similar to our results, they did not observe signi cant effects of hDPSC-derived conditioned medium (CM) on in vitro HNSCC proliferation and therapeutic sensitivity, and in vivo tumour growth, despite the increase in tumour VEGF secretion(45). Con icting results on the impact of other MSC subtypes on in vitro and in vivo HNC cell proliferation, survival, migration, invasion and therapeutic sensitivity have previously been described(46)(47)(48)(49)(50)(51)(52)(53).…”

supporting

confidence: 90%

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

Merckx

Monaco

Lambrichts

et al. 2020

Preprint

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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 efficient 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 side-effects. Nevertheless, dental pulp stromal cells (DPSCs), an MSC-like population present in teeth, could offer important clinical benefits 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 significant influence on tumour morphology, growth, angiogenesis and epithelial-to-mesenchymal transition. In addition, DPSCs migrated towards tumour cells in vitro, which could not be confirmed 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 efficacy 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.

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“…The VEGF-A amount secreted from the cells is estimated to be 206.9 pg/10 6 cells on Day 2 and increased to 389.3 pg/10 6 cells on Day 4, and slightly decreases and remains similar (287.2 pg/10 6 ) from Day 6 to Day 10. The overall increase in VEGF-A concentration is a consequence of significant increase in cell population over the culture period [69][70][71][72]. In monolayer cell culture, the cells highly proliferate and secrete more VEGF at initial stage, and the cells reach confluence afterwards and secrete less VEGF-A during the culture.…”

Section: Comparison Between Culture Formatsmentioning

confidence: 99%

Comparison of VEGF-A secretion from tumor cells under cellular stresses in conventional monolayer culture and microfluidic three-dimensional spheroid models

2020

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Vascular endothelial growth factor (VEGF) is a major cytokine in tumor biology affecting tumor survival, aggressiveness and pro-angiogenetic activities. In addition, cellular stresses often result in aggressive pro-angiogenetic behavior in tumors. For in vitro study, conventional monolayer cell culture has been broadly exploited; however, it often provides limited information due to its different microenvironment from that in vivo. Recently, three-dimensional (3D) cell spheroid culture provides in vivo-like microenvironments to study tumor biology and their survival mechanisms with better predictive power. In this work, vascular endothelial growth factor of type A (VEGF-A) secretion from osteosarcoma (MG-63) cells cultured using monolayer and 3D spheroid models under two stress conditions: nutrient deficiency (reduced serum culture) and hypoxia-inducible factor (HIF) inhibition (HIF inhibitor, YC-1) are characterized and systematically compared. In order to obtain ample sample size for consistent characterization of cellular responses from cancer spheroids under the stresses and compare the responses to those from the conventional monolayer model, a microfluidic spheroid formation and culture device is utilized in the experiments. In the analysis, cell viability is estimated from captured images, and quantification of VEGF-A secreted from the cells is achieved using enzyme-linked immunosorbent assay (ELISA). The experimental results show that the viabilities decrease when the cells face higher stress levels in both monolayer and 3D spheroid culture models; however, the VEGF-A secretion profiles between the cell culture models are different. The VEGF-A secretion decreases when the cells face higher stress conditions in the monolayer cell culture. In contrast, for the 3D spheroid culture, the VEGF-A concentration decreases for low stress levels but increases while the stress level is high. The VEGF-A regulation in the 3D models mimics in vivo cases of tumor survival and can provide insightful information to investigate tumor angiogenesis in vitro. The approach developed in this paper provides an efficient method to quantitatively and statistically study tumor growth kinetics and stress responses from highly uniform samples and it can also be applied to compare the underlying biomolecular mechanisms in monolayer and 3D spheroid culture models to elucidate the effects of microenvironments on cellular response in cancer research.

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A Study on the Effect of Human Dental Pulp Stem Cell Conditioned Medium on Human Oral Squamous Cell Carcinoma Cell Lines

Cited by 12 publications

References 38 publications

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

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

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

Comparison of VEGF-A secretion from tumor cells under cellular stresses in conventional monolayer culture and microfluidic three-dimensional spheroid models

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