title: Umbilical cord-derived mesenchymal stem cells regulate thymic epithelial cell development and function in Foxn1(-/-) mice.
abstract: Thymic microenvironments are essential for the maturation of thymocytes, which can be anatomically compartmentalized into cortical and medullar regions. The absence of the gene encoding the transcription factor forkhead box n1 (Foxn1) causes epithelial differentiation to stall in the precursor stage, resulting in the formation of an abnormal thymus. In this study, we used human umbilical cord-derived mesenchymal stem cells (UC-MSCs) to treat Foxn1(-/-) mice, and then analyzed the maturation and distribution of thymic epithelial cells in the Foxn1(-/-) thymic rudiment and the thymopoiesis of this newly developed rudiment. Our data showed a well-organized cortex-medulla architecture and an obvious improvement in the maturation of thymic epithelial cells along with the appearance of UEA-1(+)MHCII(hi) thymic epithelial cells in the rudiment. We further demonstrated improved thymopoiesis and the enhanced export of mature T cells with increased numbers of regulatory T cells into the peripheral blood. Furthermore, we observed that MSCs can engraft into thymic tissue and express many cytokines or proteins, particularly keratinocyte growth factor (KGF) and CD248, which are essential for thymic development. Collectively, our data identified a new mechanism for MSCs, which may provide a proper microenvironment for the reconstitution and functional maturation of the thymus in Foxn1(-/-) mice. Additionally, we elicited additional insights into the therapeutic efficacy of MSCs in several autoimmune diseases.
authors.affiliation: 1] Key Laboratory of Systems Bioengineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China [2] Alliancells Institute of Stem Cells and Translational Regenerative Medicine, Tianjin, China.
authors.forename: Guangyang
authors.initials: G
authors.lastname: Liu
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Graduate School of Chinese Academy of Medical Sciences and Peking Union of Medical College, Tianjin, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Graduate School of Chinese Academy of Medical Sciences and Peking Union of Medical College, Tianjin, China.
authors.forename: Tianxiang
authors.initials: T
authors.lastname: Pang
authors.affiliation: Alliancells Institute of Stem Cells and Translational Regenerative Medicine, Tianjin, China.
authors.forename: Delin
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Alliancells Institute of Stem Cells and Translational Regenerative Medicine, Tianjin, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Alliancells Institute of Stem Cells and Translational Regenerative Medicine, Tianjin, China.
authors.forename: Hanyu
authors.initials: H
authors.lastname: Wang
authors.affiliation: 1] Alliancells Institute of Stem Cells and Translational Regenerative Medicine, Tianjin, China [2] University of Florida, Department of Medicine, Gainesville, FL, USA.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Cong
authors.affiliation: Alliancells Institute of Stem Cells and Translational Regenerative Medicine, Tianjin, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D002469:Cell Separation; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology*; D051858:Forkhead Transcription Factors / Q000172:deficiency* / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology*; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; D036341:Intercellular Signaling Peptides and Proteins; C090140:Whn protein