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

Gingival Mesenchymal Stem Cells Outperform Haploidentical Dental Pulp-derived Mesenchymal Stem Cells in Proliferation Rate, Migration Ability, and Angiogenic Potential.
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DOI:
10.1177/0963689718759649
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发表时间:
2018-06
影响因子:
3.3
通讯作者:
Khoury M
Khoury M
中科院分区:
医学4区
文献类型:
--
作者:
Angelopoulos I;Brizuela C;Khoury M

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供体的高度变异使得不同牙源间的比较研究可疑。牙科组织为比较从同一供体分离的单倍体间充质干细胞(MSCs)的生物学特性提供了难得的机会。目的是通过比较牙龈(GMSCs)和牙髓干细胞(DPSCs)的单倍体同种间充质干细胞的生物学和功能,主要关注它们的血管生成潜力,来确定牙髓间充质干细胞的最佳来源。比较研究包括(1)表面标记物表达,(2)中胚层分化能力(成软骨、成脂肪和成骨),(3)增殖能力,(4)迁移潜力,(5)形成集落单位的能力,(6)体外和体内血管生成潜力。比较分析显示,在免疫表型谱和三岁分化潜力方面没有差异。第6天,GMSCs的增殖高于DPSCs(高2.6倍,P < 0.05)。与DPSCs相比,GMSCs在4、8和12 h时表现出更强的迁移能力(分别高出2.1倍、1.5倍和1.2倍,P < 0.05)。此外,两种细胞浓度下,GMSCs形成的集落单位数量均较高(150和250起始细胞分别高出1.7倍和1.4倍,P < 0.05)。与DPSCs相比,GMSCs表现出更好的血管生成能力(总管长1.17倍,总环数1.5倍,P < 0.05)。这与缺氧条件下血管生长因子的释放增强有关。最后,在评估体内血管生成的栓移植试验中,与对照(单独使用Matrigel)相比,DPSC和GMSC血红蛋白含量分别高出3.9倍和4倍。GMSCs在增殖、迁移和血管生成潜能方面优于单倍体DPSCs。这项研究将转基因干细胞定位在再生医学应用的牙科细胞来源的前沿。
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.
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