Human vascular progenitor cells used to treat diabetes ulcers

Every 30 minutes a diabetic patient loses the use of his bottom limb due to the ulceration of tissues that degenerates into a necrosis, which is a typical side effect of this disease. For this reason, finding a proper treatment able to arrest this complication is among the priorities of the scientists who study this pathology.

Paolo Madeddu, scientist of the European Vascular Genomics Network (EVGN, www.evgn.org) from the University of Bristol, in a collaborative effort with colleagues from the Istituto Besta in Milano and EVGN scientists from INSERM U441 in Bordeaux, devised an experimental model based on the administration of Vascular Progenitor Cells (VPC). In the laboratory settings the model proved to be effective on ischemic diabetic ulcers.

The research was presented today, December 13th 2006, at the Annual EVGN Conference which is taking place in Toulouse (Dec. 11-14). As they are still preliminary data, the applications of these results to man are still far in the future. However, these extremely encouraging results prompted the scientist to start a whole set of new experiments aimed at the characterization of the compounds secreted by the VPCs, which are responsible for the healing properties on diabetic ulcers.

Diabetes is a social disease that affects several million people worldwide. The ischemic ulcers it causes are lesions that damage the deepest layers of tissues, markedly reducing muscles and bones functions. Quite often, they generate infections that aggravate the conditions of already compromised patients. It’s been a few years since scientists developed an interest in the therapeutic potential of stem cells for the treatment of diabetic ulcers. In this study, however, Paolo Madeddu and colleagues used so-called Vascular Progenitor Cells. “These cells have not been fully characterized yet” explained the EVGN scientist “but we know that they display a considerable regenerative potential in the vascular environment. Besides, they are able to counteract the cellular suicide, or apoptosis”.

A major objective of the study was the creation of a diabetic model that allowed the scientists to test the regenerative capacities of VPCs. “We employed a murine model that can develop ulcers similar to those observed in humans” Madeddu said. “Then we administered a specific subpopulation of VPCs and, a week after the treatment, we checked what was the overall effect on the ulcers. We observed that the treated lesions had become thinner and smaller compared to the untreated ones, and that they were surrounded by a number of newborn capillaries, indicating that a regeneration process was ongoing”.

A further confirmation that the treatment was efficacious came from another observation: scientists noticed that VPCs stimulated cellular proliferation and inhibited cellular apoptosis, a defensive mechanism which is active also in necrotic tissues that the organism resorts to when it is unable to heal damages. Effective as well was the “conditioned medium”, that is the medium where cells were cultured, after its administration on the lesions. “The medium – underlined Madeddu – contains one or more unidentified factors that stimulate endothelial cell proliferation. Its identification will be critical for the future of this research. These and other future results could set the ground for a targeted therapy, based on the administration of progenitor cells, or in alternative, on the administration of the therapeutic compounds that they secrete.

The European Vascular Genomics Network (EVGN) is the first Network of Excellence on cardiovascular disease funded by the European Commission under the 6th Framework Programme “Life sciences, genomics and biotechnology for health” (Contract Number: LSHM-CT-2003-503254).

The Conference is supported by an unrestricted educational grant from Laboratoires SERVIER.