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Biomedical subjects

Susanna M Müller

Publications and source records attributed to Susanna M Müller.

5 recordsLinked to original sources
PubMed2006

Evidence for a functional second thymus in mice.

The thymus organ supports the development of T cells and is located in the thorax. Here, we report the existence of a second thymus in the mouse neck, which develops after birth and grows to the size of a small lymph node. The cervical thymus had a typical medulla-cortex structure, was found to support T cell development, and could correct T cell deficiency in athymic nude mice upon transplantation. The identification of a regular second thymus in the mouse may provide evolutionary links to thymus organogenesis in other vertebrates and suggests a need to reconsider the effect of thoracic thymectomy on de novo T cell production.

Animals↗
PubMed2005

Gene targeting of VEGF-A in thymus epithelium disrupts thymus blood vessel architecture.

The thymus harbors an organ-typical dense network of branching and anastomosing blood vessels. To address the molecular basis for morphogenesis of this thymus-specific vascular pattern, we have inactivated a key vascular growth factor, VEGF-A, in thymus epithelial cells (TECs). Both Vegf-A alleles were deleted in TECs by a complementation strategy termed nude mouse [mutated in the transcription factor Foxn1 (forkhead box N1)] blastocyst complementation. Injection of Foxn1(+/+) ES cells into Foxn1(nu/nu) blastocysts reconstituted a functional thymus. By dissecting thymus stromal cell subsets, we have defined, in addition to medullary TECs (mTECs) and cortical TECs (cTECs), another prominent stromal cell subset designated cortical mesenchymal cells (cMes). In chimeric thymi, mTECs and cTECs but not cMes were exclusively ES cell-derived. According to this distinct origin, the Vegf-A gene was deleted in mTECs and cTECs, whereas cMes still expressed Vegf-A. This genetic mosaic was associated with hypovascularization and disruption of the organ-typical network of vascular arcades. Thus, vascular growth factor production by TECs is required for normal thymus vascular architecture. These experiments provide insights into Foxn1-dependent and Foxn1-independent stromal cell development and demonstrate the value of this chimeric approach to analyzing gene function in thymus epithelium.

Angiography↗
PubMed2004

Allogeneic stem cell transplantation for treatment of immunodeficiency.

Primary immunodeficiencies constitute a group of highly complex congenital disorders commonly characterized by an extremely poor prognosis. Allogeneic hematopoietic stem cell transplantation has the potential to establish a permanently functioning immune system and represents a curative approach in many of these disorders. In this review several aspects of stem cell transplantation are presented, with an emphasis on the mechanism of immune reconstitution in severe combined immunodeficiency diseases. In this disorder transplant modalities vary, and also include transplantation without cytoreductive conditioning. Clinical results are summarized based on recent analysis performed in large patient cohorts, which have shown steady improvements and have led to a marked change in the prognosis of patients with primary immunodeficiencies.

Female↗
PubMed2002

HLA-haploidentical blood progenitor cell transplantation in osteopetrosis.

Infantile osteopetrosis (OP) carries an extremely poor prognosis unless treated early by hematopoietic stem cell transplantation. We explored the use of purified blood progenitor cells from HLA-haploidentical parents in 7 patients lacking suitable matched donors. Blood progenitor cells were purified by positive selection and by additional T-cell depletion using rosette formation. For conditioning, patients received busulfan, thiotepa, and either cyclophosphamide (5 patients) or fludarabine (2 patients). Stable donor engraftment developed in 6 of 7 patients. Graft-versus-host disease was not observed. Three of the 7 patients had no major complications and 4 of 7 had both veno-occlusive disease and respiratory failure. Five of 7 patients survive with complete cure of OP at a median of 4 years. Patients with OP lacking HLA-matched donors can be successfully treated by transplantation of purified blood progenitor cells from HLA-haploidentical donors.

Blood Cells↗