BONE MARROW REMODELLING IN

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SMA, arterioles) and CD34 (capillaries, sinusoids). In addition, the number and distribution of individual CD34pos progenitor cells was evaluated. In order to ...

BONE MARROW REMODELLING IN UNCOMPLICATED AND SEVERELY COMPLICATED DIABETIC PATIENTS A. Falco*, D. Madeddu*, B. Lorusso*, R. Fioretzaki*, A. Gervasi*, C. Frati*, A. Zecca*, R. Vilella***, G. Graiani**, C. Lagrasta***, G. Becchi***, L. Sambado****, M. Sambataro****, F. Quaini*. *Dept. of Clinical and Experimental Medicine, University of Parma, Parma, Italy **Dentistry School, Department of Clinical and Experimental Medicine, University of Parma Medical School, Parma, Italy. ***Dept. of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, Italy ****Department of Specialized Medicines, Endocrine, Metabolic and Nutrition Diseases Unit, Santa Maria of Ca' Foncello Hospital, Treviso, Italy Objectives: Diabetes mellitus (DM) is a global health problem resulting in multi-organ complications with cardiovascular diseases as the leading cause of diabetes-related death. Recently, both experimental models and clinical studies have shown that bone marrow (BM)-derived progenitors are functionally impaired in diabetes leading to multiple BM microenvironmental defects including microangiopathy and neuropathy. The aim of the present study was to determine whether BM remodeling in patients with diabetes is differentially affected in the presence of neurovascular complications. Materials and Methods: BM biopsies were obtained from patients affected by DM with (D-NV,n= 13) and without (D,n=10) critical neuropathy and vasculopathy. Biopsies from age and gender matched patients undergoing diagnostic procedures without relevant hematopoietic disorders were used as control (CTRL,n=15). The morphometric assessment of BM compartments was performed by histologic and immunohistochemical analyses. The volume fraction of bone, hematopoietic and fatty tissue was morphometrically determined in BM sections stained with Hematoxylin-Eosin. Vascular structures were immunohistochemically detected using specific antibodies against α-Smooth muscle actin (αSMA, arterioles) and CD34 (capillaries, sinusoids). In addition, the number and distribution of individual CD34pos progenitor cells was evaluated. In order to provide indirect evidence on the mechanism of niche remodelling and progenitors mobilization, the density and distribution in the central marrow or in the close proximity to trabecular bone were separately evaluated for each parameter. Results: As expected, the morphometric analysis displayed an increase in adipose tissue and a reduction of hematopoietic marrow in biopsies of diabetic patients when compared to CTRL. The analysis of α-SMAposvascular structures revealed changes in their density, however, an increase in paratrabecular arterioles was observed in both pathologic groups. A reduction in the amount of sinusoids was measured whereas capillaries density was found 2-fold and 5-fold increased in D group compared to CTRL and D-NV, respectively. Finally, CD34posprogenitor cells decreased in both pathologic groups while the paratrabecular fraction of this cell population was reduced only in D group. Conclusion: Our data document that a differential rearrangement of both CD34posprogenitors and vascular structures occurs in the BM of diabetic patients according to the severity of neurovascular complications. We strongly support the hypothesis that BM dysfunction is implicated in the development of multi-organ failure characteristic of advanced diabetes. Dott.ssa Angela Falco, PhD University of Parma Department of Clinical and Experimental Medicine Via Gramsci, 14 43126 Parma, Italia Tel. +39 0521 702633 Fax. +39 0521 292710