Located near the oropharynx, the tonsils are the primary mucosal immune organ. Tonsil tissue is a promising alternative source for the high-yield isolation of adult stem cells, and recent studies have reported the ide...Located near the oropharynx, the tonsils are the primary mucosal immune organ. Tonsil tissue is a promising alternative source for the high-yield isolation of adult stem cells, and recent studies have reported the identification and isolation of tonsil-derived stem cells (T-SCs) from waste surgical tissue following tonsillectomies in relatively young donors (i.e., under 10 years old). As such, TSCs offer several advantages, including superior proliferation and a shorter doubling time compared to bone marrow-derived mesenchymal stem cells (MSCs). T-SCs also exhibit multi-lineage differentiation, including mesodermal, endodermal (e.g., hepatocytes and parathyroid-like cells), and even ectodermal cells (e.g., Schwann cells). To this end, numbers of researchers have evaluated the practical use of T-SCs as an alternative source of autologous or allogenic MSCs. In this review, we summarize the details of T-SC isolation and identification and provide an overview of their application in cell therapy and regenerative medicine.展开更多
Effector B cells are central contributors to the development of autoimmune disease by activating autoreactive T cells,producing pro-inflammatory cytokines and organizing ectopic lymphoid tissue.Conversely,IL-10-produc...Effector B cells are central contributors to the development of autoimmune disease by activating autoreactive T cells,producing pro-inflammatory cytokines and organizing ectopic lymphoid tissue.Conversely,IL-10-producing regulatory B(Breg)cells have pivotal roles in maintaining immunological tolerance and restraining excessive inflammation in autoinflammatory disease.Thus,regulating the equilibrium between antibody-producing effector B cells and Breg cells is critical for the treatment of autoimmune disease.In this study,we investigated the effect of human palatine tonsil-derived mesenchymal stem cells(T-MSCs)on estradiol(E2)-induced B-cell responses in vivo and in vitro.Transplantation of T-MSC into E2-treated mice alleviated B-cell-mediated immune responses and increased the population of IL-10-producing Breg cells.T-MSCs regulated the B-cell populations by producing Epstein–Barr virus(EBV)-induced 3(EBI3),one of the two subunits of IL-35 that is the well-known inducer of Breg cells.We demonstrate a critical role of EBI3(IL-35)in vitro by depleting EBI3 in T-MSCs and by adding exogenous IL-35 to the culture system.Taken together,our data suggest that IL-35-secreting MSCs may become an attractive therapeutic to treat B-cell-mediated autoimmune diseases via expanding Breg cells.展开更多
基金Supported by the Korea Health Technology RD Project through the Korea Health Industry Development Institutethe Ministry of Health and Welfare,No.HI16C-2207+1 种基金the Basic Science Research Program through the NRF,No.NRF-2018R1D1A1A09083264Ewha Womans University,No.RP-grant2017
文摘Located near the oropharynx, the tonsils are the primary mucosal immune organ. Tonsil tissue is a promising alternative source for the high-yield isolation of adult stem cells, and recent studies have reported the identification and isolation of tonsil-derived stem cells (T-SCs) from waste surgical tissue following tonsillectomies in relatively young donors (i.e., under 10 years old). As such, TSCs offer several advantages, including superior proliferation and a shorter doubling time compared to bone marrow-derived mesenchymal stem cells (MSCs). T-SCs also exhibit multi-lineage differentiation, including mesodermal, endodermal (e.g., hepatocytes and parathyroid-like cells), and even ectodermal cells (e.g., Schwann cells). To this end, numbers of researchers have evaluated the practical use of T-SCs as an alternative source of autologous or allogenic MSCs. In this review, we summarize the details of T-SC isolation and identification and provide an overview of their application in cell therapy and regenerative medicine.
基金by the Bio&Medical Technology Development Program of the NRF funded by the Korean government(2012M3A9C6049823)In addition,this work was supported by RP-Grant 2016 of Ewha Womans University.
文摘Effector B cells are central contributors to the development of autoimmune disease by activating autoreactive T cells,producing pro-inflammatory cytokines and organizing ectopic lymphoid tissue.Conversely,IL-10-producing regulatory B(Breg)cells have pivotal roles in maintaining immunological tolerance and restraining excessive inflammation in autoinflammatory disease.Thus,regulating the equilibrium between antibody-producing effector B cells and Breg cells is critical for the treatment of autoimmune disease.In this study,we investigated the effect of human palatine tonsil-derived mesenchymal stem cells(T-MSCs)on estradiol(E2)-induced B-cell responses in vivo and in vitro.Transplantation of T-MSC into E2-treated mice alleviated B-cell-mediated immune responses and increased the population of IL-10-producing Breg cells.T-MSCs regulated the B-cell populations by producing Epstein–Barr virus(EBV)-induced 3(EBI3),one of the two subunits of IL-35 that is the well-known inducer of Breg cells.We demonstrate a critical role of EBI3(IL-35)in vitro by depleting EBI3 in T-MSCs and by adding exogenous IL-35 to the culture system.Taken together,our data suggest that IL-35-secreting MSCs may become an attractive therapeutic to treat B-cell-mediated autoimmune diseases via expanding Breg cells.