TY - JOUR
T1 - Safety and Homing of Human Dental Pulp Stromal Cells in Head and Neck Cancer
AU - Merckx, Greet
AU - Lo Monaco, Melissa
AU - Lambrichts, Ivo
AU - Himmelreich, Uwe
AU - Bronckaers, Annelies
AU - Wolfs, Esther
N1 - Funding Information:
G.M. was supported by ‘Bijzonder Onderzoeksfonds’ of Hasselt University (BOF, BOF16DOC06). M.L.M. was funded by ‘Bijzonder Onderzoeksfonds’ and ‘Fonds Spécial de Recherche’ (BOF16DOCNA02-FSR-confin UHasselt-UNamur). This research was further supported by research grants to I.L., U.H., A.B. and E.W. from the Research Foundation Flanders (‘Fonds Wetenschappelijk Onderzoek Vlaanderen (FWO)’, grant numbers G0C1916FWO, 1517916 N and G0A7514N), BOF of Hasselt University (BOF20TT04), Limburg Cancer foundation (‘Limburgs kankerfonds’ LIKAF) and KU Leuven for PF 10/017 IMIR. The funding bodies played no role in study design, data collection, analysis and interpretation, or writing of the manuscript.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2021/10
Y1 - 2021/10
N2 - 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. Graphical abstract: [Figure not available: see fulltext.]
AB - 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. Graphical abstract: [Figure not available: see fulltext.]
KW - Angiogenesis
KW - Cell survival
KW - Epithelial-to-mesenchymal transition
KW - Head and neck cancer
KW - Human dental pulp stromal cells
KW - Tumour homing
KW - Xenograft mouse model
UR - http://www.scopus.com/inward/record.url?scp=85103669896&partnerID=8YFLogxK
U2 - 10.1007/s12015-021-10159-1
DO - 10.1007/s12015-021-10159-1
M3 - Article
C2 - 33822326
AN - SCOPUS:85103669896
SN - 2629-3269
VL - 17
SP - 1619
EP - 1634
JO - Stem Cell Reviews and Reports
JF - Stem Cell Reviews and Reports
IS - 5
ER -
