Stem Cells and Healing: Impact on Inflammation.

SIGNIFICANCE: The number of patients with nonhealing wounds has rapidly accelerated over the past 10 years in both the United States and worldwide. Some causative factors at the macro level include an aging population, epidemic numbers of obese and diabetic patients, and an increasing number of surgical procedures. At the micro level, chronic inflammation is a consistent finding. RECENT ADVANCES: A number of treatment modalities are currently used to accelerate wound healing, including energy-based modalities, scaffoldings, the use of mechano-transduction, cytokines/growth factors, and cell-based therapies. The use of stem cell therapy has been hypothesized as a potentially useful adjunct for nonhealing wounds. Specifically, mesenchymal stem cells (MSCs) have been shown to improve wound healing in several studies. Immune modulating properties of MSCs have made them attractive treatment options. CRITICAL ISSUES: Current limitations of stem cell therapy include the potentially large number of cells required for an effect, complex preparation and delivery methods, and poor cell retention in targeted tissues. Comparisons of published in-vitro and clinical trials are difficult due to cell preparation techniques, passage number, and the impact of the micro-environment on cell behavior. FUTURE DIRECTIONS: MSCs may be more useful if they are preactivated with inflammatory cytokines such as tumor necrosis factor alpha or interferon gamma. This article will review the current literature with regard to the use of stem cells for wound healing. In addition the anti-inflammatory effects of MSCs will be discussed along with the potential benefits of stem cell preactivation.