Ulating the ratio of Th1/Th2 cells and secretion of immunosuppressive cytokines interleukin-10 (IL-10) and/or transforming growth factor-1 (TGF-1) [13?6]. Recently, some scientists proposed that transplantation of ex vivo expanded Tregs notTregs Improved Impaired Cognition of ADonly prevented the progression of ongoing inflammatory and autoimmune diseases in mice but also inhibited the occurrence of graft-versus-host disease after bone marrow transplantation [17]. In addition, it was reported that transplantation of autologous peripheral lymphocytes after human cord blood stem cells education in vitro could reverse the progress of T1D in clinical trial [18]. Recently, evidences indicated that abnormalities of Tregs in cell number and/or function were associated with the inflammation or pathogenesis of AD [19]. More important, it was reported that Tregs also suppressed the characteristic glial response to injury in the 16574785 CNS, assumed to be destructive to neuronal survival [20]. MSCs as multipotent nonhematopoietic progenitor cells are capable of differentiating into various lineages including osteoblasts, chondrocytes and adipocytes. In recent years, MSCs from human umbilical cord blood and bone marrow have been extensively investigated as immunomodulatory and regenerative cells in vitro and in vivo. It has been confirmed that MSCs from bone marrow and/or human umbilical cord blood Title Loaded From File display an important immunomodulatory capability via inhibiting the proliferation and function of T cells, B cells and natural killer (NK) cells as well as the function of mature monocytes-derived dendritic cells in vitro [21?3]. In addition, MSCs from bone marrow and/or human umbilical cord blood as immunomodulatory cells in vivo have been used to prevent the progression of the autoimmune and inflammatory diseases, i.e. multiple sclerosis (MS), type i diabetes (T1D), chronic colitis and experimental autoimmune uveitis via inducing the production of Tregs in vivo and/or reducing the production of pro-inflammatory factors as well as improving the production of Title Loaded From File anti-inflammatory factors [23?7] [28]. It also has been confirmed that MSCs from bone marrow and/or human umbilical cord blood can induce the phenotype expression of Treg cells or recruit Treg cells in peripheral lymphocytes in vitro [24,29]. Human umbilical cords as the clinical waste provide an alternative source for isolating plenty of MSCs [30]. It does no harm to donors and we can easily get plenty of MSCs from umbilical cords. More and more evidences demonstrate that MSCs from human umbilical cords (UC-MSCs) have the similar immuonomodulatory function as MSCs from bone marrow [31?3]. Based on these previous findings, we successfully isolated MSCs from umbilical cords. We tried to confirm whether UCMSCs can modulate the frequency and/or function of Tregs in vitro. In addition, we aimed to investigate whether systemic transplantation of Tregs after UC-MSCs education in vitro could improve the impaired cognition of APPswe/PS1dE9 transgenic mice, an animal model of AD. It is the first time to propose that autologous transplantation of purified Tregs after UC-MSCs education is used 23977191 to prevent the progress of neurodegenerative diseases, such as AD.Technology, Institute of Laboratory Animal Science, Chinese Academy of Medical Science (Beijing, China) and used throughout the study. The animals were housed in temperature- and humidity-controlled rooms and on a 12h/12h light/dark cycle. All the animal protocols.Ulating the ratio of Th1/Th2 cells and secretion of immunosuppressive cytokines interleukin-10 (IL-10) and/or transforming growth factor-1 (TGF-1) [13?6]. Recently, some scientists proposed that transplantation of ex vivo expanded Tregs notTregs Improved Impaired Cognition of ADonly prevented the progression of ongoing inflammatory and autoimmune diseases in mice but also inhibited the occurrence of graft-versus-host disease after bone marrow transplantation [17]. In addition, it was reported that transplantation of autologous peripheral lymphocytes after human cord blood stem cells education in vitro could reverse the progress of T1D in clinical trial [18]. Recently, evidences indicated that abnormalities of Tregs in cell number and/or function were associated with the inflammation or pathogenesis of AD [19]. More important, it was reported that Tregs also suppressed the characteristic glial response to injury in the 16574785 CNS, assumed to be destructive to neuronal survival [20]. MSCs as multipotent nonhematopoietic progenitor cells are capable of differentiating into various lineages including osteoblasts, chondrocytes and adipocytes. In recent years, MSCs from human umbilical cord blood and bone marrow have been extensively investigated as immunomodulatory and regenerative cells in vitro and in vivo. It has been confirmed that MSCs from bone marrow and/or human umbilical cord blood display an important immunomodulatory capability via inhibiting the proliferation and function of T cells, B cells and natural killer (NK) cells as well as the function of mature monocytes-derived dendritic cells in vitro [21?3]. In addition, MSCs from bone marrow and/or human umbilical cord blood as immunomodulatory cells in vivo have been used to prevent the progression of the autoimmune and inflammatory diseases, i.e. multiple sclerosis (MS), type i diabetes (T1D), chronic colitis and experimental autoimmune uveitis via inducing the production of Tregs in vivo and/or reducing the production of pro-inflammatory factors as well as improving the production of anti-inflammatory factors [23?7] [28]. It also has been confirmed that MSCs from bone marrow and/or human umbilical cord blood can induce the phenotype expression of Treg cells or recruit Treg cells in peripheral lymphocytes in vitro [24,29]. Human umbilical cords as the clinical waste provide an alternative source for isolating plenty of MSCs [30]. It does no harm to donors and we can easily get plenty of MSCs from umbilical cords. More and more evidences demonstrate that MSCs from human umbilical cords (UC-MSCs) have the similar immuonomodulatory function as MSCs from bone marrow [31?3]. Based on these previous findings, we successfully isolated MSCs from umbilical cords. We tried to confirm whether UCMSCs can modulate the frequency and/or function of Tregs in vitro. In addition, we aimed to investigate whether systemic transplantation of Tregs after UC-MSCs education in vitro could improve the impaired cognition of APPswe/PS1dE9 transgenic mice, an animal model of AD. It is the first time to propose that autologous transplantation of purified Tregs after UC-MSCs education is used 23977191 to prevent the progress of neurodegenerative diseases, such as AD.Technology, Institute of Laboratory Animal Science, Chinese Academy of Medical Science (Beijing, China) and used throughout the study. The animals were housed in temperature- and humidity-controlled rooms and on a 12h/12h light/dark cycle. All the animal protocols.
