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Gingival Mesenchymal Stem Cells Outperform Haploidentical Dental Pulp-derived Mesenchymal Stem Cells in Proliferation Rate, Migration Ability, and Angiogenic Potential.

ABSTRACT: High donor variation makes comparison studies between different dental sources dubious. Dental tissues offer a rare opportunity for comparing the biological characteristics of haploidentical mesenchymal stem cells (MSCs) isolated from the same donor. The objective was to identify the optimal dental source of MSCs through a biological and functional comparison of haploidentical MSCs from gingival (GMSCs) and dental pulp stem cells (DPSCs) focusing mainly on their angiogenic potential. The comparison study included (1) surface markers expression, (2) mesodermal differentiation capacity (chondrogenic, adipogenic, and osteogenic), (3) proliferation, (4) migration potential, (5) ability to form colony units, and (6) angiogenic potential in vitro and in vivo. Comparative analysis showed no difference in the immunophenotypic profile nor for the trilineage differentiation potential. Proliferation of GMSCs was higher than DPSCs at day 6 (2.6-fold higher, P < 0.05). GMSCs showed superior migratory capacity compared to DPSCs at 4, 8, and 12 h (2.1-, 1.5-, and 1.2-fold higher, respectively, P < 0.05). Furthermore, GMSCs formed a higher number of colony units for both cell concentrations (1.7- and 1.4-fold higher for 150 and 250 starting cells, respectively, P < 0.05). GMSCs showed an improved angiogenic capacity compared to DPSCs (total tube lengths 1.17-fold higher and 1.5-fold total loops, P < 0.05). This was correlated with an enhanced release of vascular growth factor under hypoxic conditions. Finally, in the plug transplantation assay evaluating the angiogenesis in vivo, the DPSC and GMSC hemoglobin content was 3.9- and 4-fold higher, respectively, when compared to the control (Matrigel alone). GMSCs were superior to their haploidentical DPSCs in proliferation, migration, and angiogenic potentials. This study positions GMSCs in the forefront of dental cell sources for applications in regenerative medicine.

SUBMITTER: Angelopoulos I

PROVIDER: S-EPMC6050910 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundDental pulp stem cells (DPSCs) have been developed as a potential source of mesenchymal stem cells (MSCs) for regeneration of dental pulp and other tissues. However, further strategies to isolate highly functional DPSCs beyond the colony-forming methods are required. We have demonstrated the safety and efficacy of DPSCs isolated by G-CSF-induced mobilization and cultured under normoxia (mobilized DPSCs, MDPSCs) for pulp regeneration. The device for isolation of MDPSCs, however, is not cost-effective and requires a prolonged cell culture period. It is well known that MSCs cultured under hypoxic-preconditions improved MSC proliferation activity and stemness. Therefore, in this investigation, we attempted to improve the clinical utility of DPSCs by hypoxia-preconditioned DPSCs (hpDPSCs) compared with MDPSCs to improve the potential clinical utility for pulp regeneration in endodontic dentistry.MethodsColony-forming DPSCs were isolated and preconditioned with hypoxia in a stable closed cultured system and compared with MDPSCs isolated from the individual dog teeth. We examined the proliferation rate, migration potential, anti-apoptotic activity, and gene expression of the stem cell markers and angiogenic/neurotrophic factors. Trophic effects of the conditioned medium (CM) were also evaluated. In addition, the expression of immunomodulatory molecules upon stimulation with IFN-γ was investigated. The pulp regenerative potential and transplantation safety of hpDPSCs were further assessed in pulpectomized teeth in dogs by histological and immunohistochemical analyses and by chemistry of the blood and urine tests.ResultshpDPSCs demonstrated higher proliferation rate and expression of a major regulator of oxygen homeostasis, HIF-1α, and a stem cell marker, CXCR-4. The direct migratory activity of hpDPSCs in response to G-CSF was significantly higher than MDPSCs. The CM of hpDPSCs stimulated neurite extension. However, there were no changes in angiogenic, migration, and anti-apoptotic activities compared with the CM of MDPSCs. The expression of immunomodulatory gene, PTGE was significantly upregulated by IFN gamma in hpDPSCs compared with MDPSCs. However, no difference in nitric oxide was observed. The regenerated pulp tissue was quantitatively and qualitatively similar in hpDPSC transplants compared with MDPSC transplants in dog teeth. There was no evidence of toxicity or adverse events of the hpDPSC transplantation.ConclusionsThese results demonstrated that the efficacy of hpDPSCs for pulp regeneration was identical, although hpDPSCs improved stem cell properties compared to MDPSCs, suggesting their potential clinical utility for pulp regeneration.

Project description:UnlabelledMesenchymal stem cells (MSCs) of placental origin have become increasingly translational owing to their abundance and accessibility. MSCs of different origin share several features but also present biological differences that might point to distinct clinical properties. Hence, mixing fetal and maternal cells from the same placenta can lead to contradicting results. We analyzed the biological characteristics of haploidentical MSCs isolated from fetal sources, including the umbilical cord (UC-MSCs) and chorion (Ch-MSCs), compared with maternal decidua MSCs (Dc-MSCs). All MSCs were analyzed for general stem cell properties. In addition, immunosuppressive capacity was assessed by the inhibition of T-cell proliferation, and angiogenic potential was evaluated in a Matrigel transplantation assay. The comparison between haploidentical MSCs displayed several distinct features, including (a) marked differences in the expression of CD56, (b) a higher proliferative capacity for Dc-MSCs and UC-MSCs than for Ch-MSCs, (c) a diversity of mesodermal differentiation potential in favor of fetal MSCs, (d) a higher capacity for Ch-MSCs to inhibit T-cell proliferation, and (e) superior angiogenic potential of Ch-MSCs evidenced by a higher capability to form tubular vessel-like structures and an enhanced release of hepatocyte growth factor and vascular endothelial growth factor under hypoxic conditions. Our results suggest that assessing the prevalence of fetomaternal contamination within placental MSCs is necessary to increase robustness and limit side effects in their clinical use. Finally, our work presents evidence positioning fetoplacental cells and notably Ch-MSCs in the forefront of the quest for cell types that are superior for applications in regenerative medicine.SignificanceThis study analyzed the biological characteristics of mesenchymal stem cells (MSCs) isolated from fetal and maternal placental origins. The findings can be summarized as follows: (a) important differences were found in the expression of CD56, (b) a different mesodermal differentiation potential was found in favor of fetal MSCs, (c) a higher immunosuppressive capacity for chorion MSCs was noted, and (d) superior angiogenic potential of Ch-MSCs was observed. These results suggest that assessing the prevalence of fetomaternal contamination within placental MSCs is necessary to increase robustness and limit side effects in their clinical use. The evidence should allow clinicians to view fetoplacental cells, notably Ch-MSCs, favorably as candidates for use in regenerative medicine.

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Gingival Mesenchymal Stem Cells Outperform Haploidentical Dental Pulp-derived Mesenchymal Stem Cells in Proliferation Rate, Migration Ability, and Angiogenic Potential.

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