The Role of Recombinant TGF-β in the Function of eEPCs, in Healthy and Diabetic Patients

Hagai Yavin , Dorit Leshem-Lev Oshrat Dadush Ran Kornowski Eli Lev
Cardiolegy, Rabin medical center, Petah tiquwa, israel, Israel

Introduction: Recent evidence has shown that endothelial progenitor cells (EPCs) have an important role in repair process following vascular injury, and that in patients with diabetes EPC number and function are significantly reduced. Transforming growth factor-β (TGF-β) is a growth factor which has a role in regulation of vessel endothelium. TGF-β is located in platelets` alpha granules and released upon activation. Recently our group demonstrated that EPCs functionality was enhanced after co-incubated with activated platelets, and attenuated by the TGFβRII inhibitor. We therefore, aimed to further explore the association between TGF-β and EPCs, by examining thein vitro the effects of recombinant TGF-β on the differentiation and function of EPCs from both healthy and diabetic patients. Our hypothesis was that recombinant TGF-β will improve the functional and proliferative aspects of EPCs.

Methods: Human EPCs were isolated from peripheral blood of 10 healthy volunteers and 10 DM patients, and cultured for 7 days with and without recombinant TGF-β.  EPCs functional properties were evaluated by their capacity to form colonies (tested by using an inverted microscope), to proliferate (examined by the MTT assay and to differentiate (expression of the mature endothelial markers Tie-2 and VE-cadherin, evaluated by FACS).

Results: After 7 days of culture, cell viability, the expression of endothelial markers and the capacity to form colonies, were lower in EPCs co-incubated with recombinant TGF-β (compared with incubation without TGF-β), both in the healthy individuals and DM patients.

Conclusion: Contrary to our hypothesis, recombinant TGF-β, by itself, is insufficient to regulate functional and proliferative aspects of EPCs, and in fact seems to attenuate EPCs, both in healthy and in DM pateints.









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