The Effect of Human Adipose-Derived Stem Cells on Healing of Ischemic Wounds in a Diabetic Nude Mouse Model

Abstract

This study demonstrated the beneficial effect of human adipose-derived stem cells on healing of ischemic wound in diabetic nude mice. Elevation of vascular endothelial growth factor levels in plasma and tissue suggests the importance of secretory factor, which regulates local angiogenesis and triggers a systemic response.

Adipose-Derived Stem Cells in Tissue Regeneration: A Review

“…Increased VEGF expression, together with increased collagen density and microvascular density, is also measured in fill-thickness rat skin grafts injected with ASCs [327]. VEGF secretion by ASCs is significantly upregulated in vitro upon metabolic induction of ischemia [328] and ischemic limbs in diabetic nude mice treated with ASCs show earlier and more abundant neovessel formation, together with increased levels of plasma VEGF [303]. Inhibition of VEGF secretion by ASCs through RNA interference (RNAi), followed by their transplantation into syngeneic models of small-for-size liver injury results in significant disturbances to graft microcirculation, serum liver functional parameters, and graft survival [329].…”

“…Consistent with this, vessel formation has been observed in several ASC models of cardiac infarct treatment, epithelial regeneration, and neural tissue healing (discussed above). In addition, multiple studies of ischemia describe increased vascularization following ASC administration [145,150,[297][298][299][300][301][302][303]. Hemodynamic abnormalities in pulmonary arterial hypertension may be reversed using ASCs-a finding thought to be attributable to their induction of angiogenesis and increased formation of small, ISRN Stem Cells pulmonary arteries [304].…”

“…For example, both in vitro and in vivo studies suggest that the ASC drives endothelial differentiation and stabilizes it through paracrine action [317]. As a candidate for mediating vessel formation, the most obvious paracrine factor is VEGF and many studies propose that it is the secretion of VEGF as the underlying reason for the improved vascularization by the ASCs [303,306,315,[318][319][320][321]. The ability of VEGF to stimulate neoangiogenesis is well known [322][323][324] and the secretion of VEGF by ASCs under normal and abnormal conditions (i.e., hypoxia) has been reported by many as the factor underlying ASC-mediated angiogenesis [145,184,318,325,326].…”

Stem cells and chronic wound healing: state of the art

“…21 Administering heterogeneous groups of stem cells may allow for communication between different cell types, facilitating improved tissue regeneration, as is seen with coculture of MSCs together with EPCs. 22 Applied to chronic wound therapies, both MSCs 23,24 and ASCs 25 have demonstrated an ability to improve wound healing in experimental diabetic models. Findings from in vitro experiments have elucidated a number of ways that BM-MSCs promote tissue regeneration, including production of growth factors, cytokines, collagens, and matrix metalloproteinases.…”

In vivo determination of muscle-derived stem cells in rat corpus cavernosum

“…These exogenous cells include embryonic stem cells, mesenchymal stem cells, adipose stem cells, muscle-derived stem cells, neural crest stem cells, and other stem cells (Jackson et al, 2007). Although there are a multitude of exogenous cells that can be used, the development of these cells has been limited due to the complexity and invasiveness of the treatment process (Ambrosio et al, 2009;Kim et al, 2011b). Non-invasive methods and investigations into the expression of endogenous stem cells in cavernosum are paramount to successful cellular ED interventions (Song et al, 2007).…”