An unexplained paradox puzzles diabetologists: diabetic patients must face both poor vessel growth in ischemic heart and limbs and increased angiogenesis in retinal complications (1,2). Endothelial progenitor cells (EPCs) are marrow-derived cells involved in adult neovascularization and endothelial homeostasis (3,4). It has been postulated that low EPCs in peripheral blood may have a role in cardiovascular disease, and we have demonstrated that EPCs are reduced in macrovascular diabetes complications (5,6). On the other hand, an excess of EPCs may be involved in pathologic neoangiogenesis of cancer and proliferative retinopathy (7,8). Therefore, diabetes complications may be associated with both decreased and increased EPCs. Recently, novel therapeutic approaches have been directed to enrich the EPC pool in ischemic diseases and to block EPC function in proliferative diseases (9,10). These approaches in diabetic subjects require cautious evaluation of the implications carried by the paradox and new studies to unravel its causes (11,12). This study was carried out to investigate the contemporaneous effects of retinal and peripheral vascular complications on circulating progenitor cells. Ethics committee approval was obtained, and after giving informed consent, 60 type 2 diabetic patients were prospectively included. Patients were characterized in terms of peripheral arterial disease (PAD) and diabetic retinopathy (DR) as the most representative complications at the two extremities of the diabetic paradox. PAD was diagnosed by minimal criteria (including history of claudication or rest pain, pulse examination, ankle-brachial indexes, and ultrasonography) and eventually confirmed by angiography. Diabetic retinopathy (severe nonproliferative or proliferative) was defined by a dilated and comprehensive eye examination and acquisition of high-quality stereoscopic photographs by …

Objective: Transplantation of stem cells in the acute ischemic myocardium (AMI) may play a rote in the recovery of cardiac function. Here, we investigated the ability of amniotic fluid-derived mesenchymal cells (AFC) for phenotypic conversion to vascular cells and cardiomyocytes (CM) when autotransplanted in a porcine model of AMI. Methods: Single AFC preparations were taken from 12 fetuses 3 days before normal delivery. AFC were expanded in vitro and stored separately until animals of the original litter weighed 22-25 kg. A new model of AMI, i.e. 45-min circumflex coronary occlusion followed by watt dissection, was used to assess AFC differentiation potential. CMFDA-labeled AFC were autogenically transplanted in the ischemic area I week after AMI induction. Thirty days Later, pigs were sacrificed and the phenotypic profile of transplanted AFC was assessed and compared to the corresponding pre-injection pattern. Results: AFC showed in vitro to be of mesenchymal type also expressing markers of 'embryonic stem' cells (SSEA4 and Oct-4), as well as endothelial (von Willebrand factor, VE-cadherin) and smooth muscle (SM alpha-actin, SM22) cells. Thirty days after transplantation, in the survived AFC (5 +/- 1%) 'embryonic stem' cell markers disappeared and mesenchymal cell markers were down regulated with the exception of smooth muscle and endothelial antigens. No evidence for expression of cardiac troponin I was found. Conclusions: In the conditions used in this study, AFC were able to transdifferentiate to cells of vascular cell lineages but not to CM. Thus, porcine AFC may require further ex vivo re-programming to be suitable for therapeutic use in AMI. (c) 2005 Elsevier B.V. ALL rights reserved.