Chronic venous leg ulcers: the role of fibrosis, stem cells and tissue regeneration

INTRODUCTION: Chronic venous leg ulcer (CVLU) arises from the more severe state of chronic venous disease (CVD) and is a major cause of morbidity, affecting patients' quality of life and also having serious economic consequences for national health care systems due to the significant costs associated with treatment. The pathophysiology of CVLU is complex, resulting from venous hypertension, genetic anomalies, cellular and cytochemical events and alteration of the extracellular matrix. The present review discusses a detailed and updated thematic article on fibrosis, stem cells and tissue regeneration in the field of CVLU. EVIDENCE ACQUISITION: We planned to include all the studies dealing with "chronic venous leg ulcers" and "fibrosis" and "stem cells." We excluded all the studies, which did not properly fit our research question, and with insufficient data. EVIDENCE SYNTHESIS: Of the 112 records found, after removing of duplicates, and after records excluded in title and abstract, 39 matched our inclusion criteria. After reading the full-text articles, we decided to exclude 15 articles because of the following reasons: 1) not responding properly to our research questions; 2) insufficient data; the final set included 24 articles. CONCLUSIONS: Dermal tissue fibrosis and extracellular matrix (ECM) alterations are the predominant abnormalities, which are present in the stages that precede venous ulceration. Mesenchymal stem cells (MSCs) have been extensively studied for clinical implementation in this field, as they may have important roles in modulating complex signaling networks and actively participating in the different phases of wound healing.