Endothelial progenitor cells (EPCs) are endothelial precursors involved in the revascularization of injured tissue and tissue repair (4). Their vascular repairing potentials have been reported in a variety of preclinical and clinical studies with ischemic diseases, including myocardial infaction, stroke and peripheral arterial disease (5). In addition, several publications including ours reported that EPC transplantation accelerated wound healing by enhancing neovascularization in granulation tissue. Suh et al. reported that the intradermally injected EPCs secreted a variety of wound healing-related growth factors and cytokines, thereby promoting the recruitment of monocyte/macrophage and stimulating endogenous angiogenesis during the wound healing process (6). Barcelos et al. reported that the transplantation of human CD133⁺ progenitor cells into streptozotocin-induced diabetic mice, increased the wound closure rate and the capillary density in the granulation tissues (7). Another study showed that the treatment of ischemic hindlimb with EPC-conditioned medium (EPC-CM) leaded to a substantial increase in blood flow in the presence of enhanced neovascularuzation, vascular maturation and muscle function. Recently, Di Santo et al. reported that the regenerative potential of EPC-CM was equivalent to that achieved by EPC transplantation, suggesting that EPC-CM might serve as another therapeutic option that is free from allograft-associated immune rejection concern (8). These results suggested that EPC transplantation could be beneficial for the treatment of cutaneous wounds, especially chronic wounds that are often associated with decreased peripheral blood flow and remain difficult to heal using current therapeutic approaches.

Bone marrow-derived mesenchymal stem cell (BMMSCs), also referred to as stromal progenitor cell, is another promising candidate to repair or replace damaged tissues (9). They have been known to have ability to differentiate into multiple lineages, such as endothelial cells (10, 11), neural cells (12), hepatocytes (13) and others. In addition, Mikako et al. recently show that BM-MSCs contributed to wound repair by differentiating into multiple skin cell types (14). In this study, BM-MSCs were able to differentiate into keratinocytes, endothelial cells, pericytes and monocytes. In 2007, Wu et al. reported that BM-MSCs significantly enhanced wound healing in both diabetic and nondiabetic mice, in that BM-MSC-treated wounds exhibited accelerated wound closure by releasing proangiogenic factors such as VEGF and angiopoietin-1 (15). Analysis of paracrine factors released from BM-MSCs with real-time PCR and of BM-MSC-CM by ELISA showed that BM-SMCs secreted VEGF, IGF-1, EGF, KGF, angiopoietin-1, and stromal derived factor-1. These paracrine factors from MSC-CM made a great contribution in recruiting CD14⁺ monocytes, keratinocytes and endothelial cells into wounded tissues, thereby promoting the wound healing process (16).

Adipose tissue-derived stem cells (ADSCs) are located within the stromal vascular fraction of adipose tissue. ADSCs have the potential to differentiate into adipogenic, osteogenic, chondrogenic, and myogenic cells when they are cultured in specific culture conditions. Recent reports described the potential impact of ADSCs on neovascularization in ischemic disease animal models. ADSCs have been shown to release many potent angiogenic factors and also to be incorporated into blood vessels through differentiating into endothelial cells in in vivo study (17–19). In 2009, Ebrahimian et al. reported the transplantation of ADSCs promoted wound closure and improved the blood perfusion in the wounded skin (20). When ADSCs were cultured in hypoxic conditions, they secreted VEGF 5-fold more than in normoxic condition. Conditioned media obtained from hypoxic ADSCs significantly increased endothelial cell growth and reduced endothelial cell apoptosis (21).