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 2/2 mice, and then analyzed the maturation and distribution of thymic epithelial cells in the Foxn1 2/2 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 1 MHCIIhi 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 2/2 mice. Additionally, we elicited additional insights into the therapeutic efficacy of MSCs in several autoimmune diseases.

(Mesenchymal) Stem Cell-Based Therapy in Cisplatin-Induced Acute Kidney Injury Animal Model: Risk of Immunogenicity and Tumorigenicity

“…It is important to take into consideration that athymia is associated with profound immunodeficiency, but restitution of thymus leads to the improvement of the immune system [ 67 ]. Restitution of thymus integrity and function (which was in our case diminished following ATG and cisplatin treatment) was already described after MSC therapy [ 68 ]. Moderate chronic jejunitis and focal infiltration of mononuclear cells in lungs and kidneys found in the mouse after MSC therapy may suggest that immunoregulatory properties of transplanted MSCs together with timely vanishing effect of ATG-enabled immune system awakening and resulted in the occurrence of dispersed inflammatory changes.…”

Immunogenicity of allogeneic mesenchymal stem cells transplanted via different routes in diabetic rats

“…These results suggest that MSCs may shift the balance of T-cell subsets from pro-inflammatory to anti-inflammatory, as described previously. 28 According to Liu et al, 29 these immunomodulatory effects may be due to MSC secretion of various cytokines, especially KGF, to modulate the thymic microenvironment. These immunological changes may contribute to the reduction of inflammatory injury of b cells and restored BG homeostasis, although other mechanisms may be involved in the process, such as the secretion of bioactive factors (IL-6, HGF, TGF-b1, SDF-1, VEGF, IL-1b, PGE) and reduction of systemic oxidative stress.…”

Mesenchymal stem cell transplantation improves chronic colitis-associated complications through inhibiting the activity of toll-like receptor-4 in mice

“…The hUC-MSCs were kindly provided by Alliancells Bioscience Co, Ltd. of Tianjin, China. The hUC-MSCs were isolated and expanded by the company, based on a published method [ 23 , 24 ]. Flow cytometry was used to analyze and identify the MSC phenotype, as previously described [ 23 ].…”

“…Histopathological scores of colons were assigned in a blinded manner by two trained animal pathologists. A scoring system that focused on inflammatory cell infiltration and mucosal damage was used, as previously described [ 24 ].…”