Nörofibromatozis Tip 1(Nf1) Kaynaklı Mezenkimal Stromal Hücrelerin Detaylı Karakterizasyonu

Abstract

Neurofibromatosis type 1 (NF1) is an inherited autosomal dominant disease characterized by mutation in the neurofibromin (NF1) tumor suppressor gene. The lack of neurofibromin, the gene product, causes defects in the nervous system, affects intracellular mitogenic signaling, induces alterations in cell proliferation and differentiation leading to increased tendency in the development of neoplasm. The most common tumors are neurofibromas, the complex tumors derived from Schwann cells containing fibroblasts, rich vascular structures and mast cells. There are epidermic and subcutaneous neurofibromas and besides there are plexiform neurofibromas which can develop into malignant tumors and -according to their localization- lead to functional problems. Other clinical findings in NF1 include bone defects, bleeding diathesis, delayed wound healing and susceptibility to leukemia. This study was designed to investigate the contribution of mesenchymal stem/stromal cells (MSC)/Fibroblasts as the microenvironmental elements, to the occurrence or progression of the clinical symptoms of NF1. Mesenchymal Stem Cells/Fibroblasts which are supportive cells of stromal character, affect the biological behaviour of other cells such as proliferation, apoptosis and migration through various secreted growth factors, cytokines, chemokines, by direct or indirect contact. The MSC/Fibroblasts of NF1 patients can be different from those of normal individuals in terms of differentiation and survival time due to the mutation they carry. In this study, we planned to analyze the effect of mesodermal derived cells the MSC/Fibroblast of NF1 patients on microenvironment and pathogenesis of NF1. MSC/fibroblasts were expanded from biological materials of patients and healthy donors, and characterized in detail. Their adipogenic, osteogenic differentiation potential and wound healing capacity were compared, additionally, MSC-Schwann cell interaction was investigated in co-culture. All of these studies were performed on biological materials derived from NF1 patients with dermal and plexiform neurofibromas and the characteristics of MSC/Fibroblasts derived from each patient’s café au lait, healthy and neurofibrom tissues were determined.