Activated mesenchymal stem cells increase wound tensile strength in aged mouse model via macrophages

Background: Wound healing is impaired in the aged. Mesenchymal stem cells (MSCs) can exert beneficial effects in wounds; however, promoting healing in the challenging setting of aged skin may require additional potency. MSCs can enhance the production of proregenerative cytokines and growth factors when activated with interferon gamma. We hypothesized that the increased potency of activated MSC could be used to facilitate wound healing in the aged mice. Methods: Young and old C57BL6 mice underwent incisional wounds and were treated with naive MSCs, activated MSCs, or vehicle to examine MSC effects on tensile strength in the aged skin. To test whether the benefits of MSC treatment could be attributed to the participation of host macrophages, liposomal clodronate was used to deplete host macrophages. Results: In older mice, tensile strength of healing wounds was significantly lower than that in younger mice. Older mice treated with activated MSCs showed significant increases in tensile strength restoring the strength to that observed in younger mice. Macrophage depletion abrogated the beneficial effect of MSC. Conclusions: Activated MSCs restored wound tensile strength in the aged mice, and this effect was dependent on host macrophage activity. These data provide encouraging support for the development of activated MSC therapies for enhanced tissue regeneration, especially for older population groups. (C) 2013 Elsevier Inc. All rights reserved.