Inborn errors of thymic stromal cell development and function

Journal article

Physical interaction of multipotent stromal cells (MSCs) and hematopoietic stem cells (HSCs) is a modern approach to effective and focused changes in the properties of HSCs. Resulting of those contact interaction is significant activation of cells with following immune system restoration. The purpose of the study is to investigate the effect of co-transplantation of bone marrow hematopoietic stem cells (HSCs) and thymic multipotent stromal cells (MSCs) separately and as a union of cells on regeneration of the murine immune system, damaged by cyclophosphamide. MSCs were obtained from thymuses of C57BL mice using explant technique. Bone marrow cells (BMCs) were obtained by flushing out the femur with a nutrient medium. BMCs were cocultivated for 2 hours on the monolayer of thymus-derived MSCs. The immune deficiency of mice was modelled by the treatment with cyclophosphamide (CP). After that, the cells were co-transplanted in two methods (separately into different the retroorbital sinus and as a union after co-cultivation) and the parameters of the immune system were evaluated. It was shown, that separate co-transplantation of BMCs and thymus-derived MSCs is associated with the restoration of the number of bone marrow cells, thymus, spleen and lymph nodes with an increase in the proliferation index of lymph node cells by 1.4 times compared to control. It normalized the previous reduced concentration of hemoglobin and hematocrit in the blood. Co-transplantation had a suppressive effect on the blast transformation reaction, induced by phytohemagglutinin, by 4.3 times, but showed a stimulating effect on DTHR response by 1.6 times compared to control. Co-transplantation of the union of BMCs and MSCs is associated with the restoration of the number of bone marrow cells, spleen and lymph nodes. The level of spontaneous apoptosis of lymph node cells significantly increased by 3.3 times compared to control. It had not effect on hematological parameters, but is activated to impact the immune system. Thus, as a result of cells union administration showed normalization of the bactericidal activity of peritoneal macrophages, unlike the separate co-transplantation. This cells graft had a suppressive effect on the number of antibody-producing cells in the spleen by 4.2 times compared to control. Previous co-cultivation and contact interaction of cells change the properties of cell graft. The effect of co-transplantation of BMCs and thymic MSCs is not a simple additive effect of cells. It is acquiring the features typical to certain cell types, and the expression of new characteristics. We assume this phenomenon as a result development of complex cells cooperative processes in vivo and in vitr

Authors: Kreins, AY; Maio, S; Dhalla, F

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer
• Journal: Seminars in Immunopathology
• Volume: 43
• Issue: 1
• Pages: 85-100
• Publication date: 2020-11-30
• DOI: 10.1007/s00281-020-00826-9
• EISSN: 1863-2300
• ISSN: 1863-2297
• Language: English
• Keywords: Biology; Internal medicine; Pathology; Immune system; Mesenchymal stem cell; T cell; Immunology; Cancer research; Primary immunodeficiency; Autoimmunity; Genetics; Immunodeficiency; Medicine; Cell biology; Stromal cell; Transplantation; Pharyngeal pouch