Liu Y, Wang L, Liu S, Liu D, Chen C, Xu X, Chen X, Shi S
Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA Department of Pediatric Dentistry, School of Stomatology, China Medical University, Shenyang, China.
Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA.
J Dent Res. 2014 Nov;93(11):1124-32. doi: 10.1177/0022034514552675. Epub 2014 Sep 24.
Stem cells from human exfoliated deciduous teeth (SHED) are a unique postnatal stem cell population, possessing multipotent differentiation capacity and immunomodulatory properties. However, the mechanism by which SHED treat immune diseases is not fully understood. Here we show that systemic transplantation of SHED via the tail vein ameliorates ovariectomy (OVX)-induced osteopenia by reducing T-helper 1 (Th1) and T-helper 17 (Th17) cell numbers in the recipient OVX mice. Mechanistically, SHED transplantation induces activated T-cell apoptosis in OVX mice via Fas ligand (FasL)-mediated Fas pathway activation, leading to up-regulation of regulatory T-cells (Tregs) and down-regulation of Th1 and Th17 cells. This SHED-mediated immunomodulation rescues OVX-induced impairment of bone marrow mesenchymal stem cells (BMMSCs) and activation of osteoclastogenesis, resulting in increased bone mass. In summary, SHED-mediated T-cell apoptosis via a FasL/Fas pathway results in immune tolerance and ameliorates the osteopenia phenotype in OVX mice.
人脱落乳牙干细胞（SHED）是一种独特的出生后干细胞群体，具有多能分化能力和免疫调节特性。然而，SHED治疗免疫疾病的机制尚未完全阐明。在此我们表明，通过尾静脉进行SHED的全身移植，可通过减少受体去卵巢（OVX）小鼠中的辅助性T细胞1（Th1）和辅助性T细胞17（Th17）数量，改善去卵巢诱导的骨质减少。机制上，SHED移植通过Fas配体（FasL）介导的Fas途径激活，诱导OVX小鼠中活化的T细胞凋亡，导致调节性T细胞（Tregs）上调以及Th1和Th17细胞下调。这种SHED介导的免疫调节挽救了OVX诱导的骨髓间充质干细胞（BMMSC）损伤和破骨细胞生成激活，从而增加骨量。总之，SHED通过FasL/Fas途径介导的T细胞凋亡导致免疫耐受，并改善OVX小鼠的骨质减少表型。
