Capillary Regeneration in Scleroderma: Stem Cell Therapy Reverses Phenotype?
| Autor: | Daniel E. Furst, Gretchen Henstorf, Howard M. Shulman, David Fiorentino, Jerry A. Molitor, Richard A. Nash, Robert Lafyatis, Stephen M. Schwartz, David K. Pritchard, Jo Nadine Fleming, D. O. McLeod, M. Kari Connolly, Lawrence D. Adams |
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| Rok vydání: | 2008 |
| Předmět: |
Pathology/Histopathology
Pathology medicine.medical_specialty Dermatology/Skin and Systemic Disease Cardiovascular Disorders medicine.medical_treatment Immunology/Innate Immunity Cell Biology/Cell Growth and Division Immunology/Immunomodulation lcsh:Medicine Dermatology Disease Cell Biology/Cell Signaling Scleroderma Rheumatology Dermis Biopsy Humans Regeneration Medicine Cardiovascular Disorders/Vascular Biology Cell Biology/Leukocyte Signaling and Gene Expression lcsh:Science skin and connective tissue diseases Rheumatology/Autoimmunity Autoimmune and Inflammatory Diseases Autoimmune disease Multidisciplinary integumentary system medicine.diagnostic_test business.industry Regeneration (biology) lcsh:R Cell Biology/Cellular Death and Stress Responses Stem-cell therapy medicine.disease Phenotype Capillaries stomatognathic diseases medicine.anatomical_structure Scleroderma Diffuse Immunology/Immune Response Immunology lcsh:Q Rheumatology/Connective Tissue Disease business Stem Cell Transplantation Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 3, Iss 1, p e1452 (2008) |
| ISSN: | 1932-6203 |
| Popis: | Background Scleroderma is an autoimmune disease with a characteristic vascular pathology. The vasculopathy associated with scleroderma is one of the major contributors to the clinical manifestations of the disease. Methodology/Principal Findings We used immunohistochemical and mRNA in situ hybridization techniques to characterize this vasculopathy and showed with morphometry that scleroderma has true capillary rarefaction. We compared skin biopsies from 23 scleroderma patients and 24 normal controls and 7 scleroderma patients who had undergone high dose immunosuppressive therapy followed by autologous hematopoietic cell transplant. Along with the loss of capillaries there was a dramatic change in endothelial phenotype in the residual vessels. The molecules defining this phenotype are: vascular endothelial cadherin, a supposedly universal endothelial marker required for tube formation (lost in the scleroderma tissue), antiangiogenic interferon α (overexpressed in the scleroderma dermis) and RGS5, a signaling molecule whose expression coincides with the end of branching morphogenesis during development and tumor angiogenesis (also overexpressed in scleroderma skin. Following high dose immunosuppressive therapy, patients experienced clinical improvement and 5 of the 7 patients with scleroderma had increased capillary counts. It was also observed in the same 5 patients, that the interferon α and vascular endothelial cadherin had returned to normal as other clinical signs in the skin regressed, and in all 7 patients, RGS5 had returned to normal. Conclusion/Significance These data provide the first objective evidence for loss of vessels in scleroderma and show that this phenomenon is reversible. Coordinate changes in expression of three molecules already implicated in angiogenesis or anti-angiogenesis suggest that control of expression of these three molecules may be the underlying mechanism for at least the vascular component of this disease. Since rarefaction has been little studied, these data may have implications for other diseases characterized by loss of capillaries including hypertension, congestive heart failure and scar formation. |
| Databáze: | OpenAIRE |
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