Skin Microcolumns as a Source of Paracrine Signaling Factors

Abstract

We recently developed the approach of using ''microcolumns'' of autologous full-thickness skin tissue for wound repair. The small size of these micro skin tissue columns (MSTCs, *0.5 mm in diameter) allows donor sites to heal quickly without scarring. Treatment with MSTCs significantly accelerate wound healing, and suppled various skin cell types and skin structures to replenish the wound volume. This technology is now starting clinical use. In this study, we investigate whether MSTCs may also influence wound healing by releasing soluble signaling factors. Approach: Freshly harvested MSTCs were incubated in culture medium for 24 h. The conditioned medium was collected and tested for its effects on migration and proliferation of human dermal fibroblasts, and its ability to induce tube formation by human umbilical vein endothelial cells (HUVECs). Proteins released into the conditioned medium were characterized by multiplex enzymelinked immunosorbent assay (ELISA), and compared with medium conditioned by an equivalent mass of intact full-thickness skin. Results: MSTC-conditioned medium increased fibroblast migration and proliferation, as well as HUVEC tube formation. MSTCs released many soluble factors known to play prominent roles in wound healing. A subset of proteins showed significantly different release profiles compared with intact full-thickness skin. Innovation: The technology for harvesting and using MSTCs to augment wound healing was recently developed as an alternative to conventional autologous skin grafting. This study shows that MSTCs could also function as ''cytokine factories.'' Conclusion: In addition to supplying autologous cells to repopulate the wound volume, MSTCs can also function as a source of growth factors and cytokines to further enhance wound healing.

Full‐thickness skin columns: A method to reduce healing time and donor site morbidity in deep partial‐thickness burns

“…Adnexal structures such as hair follicles, eccrine glands and rete ridges contained within these columns allow the wounds to heal from within, rather than from the wound edges when full‐thickness wounds damage these important structures 32 . The inherent paracrine signalling within these skin microcolumns has also been found to have a potent stimulatory effect on wound healing, an added benefit to applying autologous skin columns to wounds 33 …”

“…32 The inherent paracrine signalling within these skin microcolumns has also been found to have a potent stimulatory effect on wound healing, an added benefit to applying autologous skin columns to wounds. 33 In addition to the implantation of FTSCs directly into the wound bed, we were also interested in determining the maximum amount of skin columns that could be harvested from a donor site while maintaining the integrity of the skin, and whether or not this affected donor site morbidity. As compared to STSGs.…”

MagneTEskin—Reconstructing skin by magnetically induced assembly of autologous microtissue cores

“…Structural components of the skin, such as collagen and elastin networks, seem more likely for this role, and changes in mechanical properties when these extracellular networks are disrupted may be a contributing factor, as mechanotransduction pathways are known to be key mediators influencing long-term scarring versus regeneration in skin wounds (28). We have previously shown that MSTCs exhibited an altered paracrine production profile compared to FTSGs (29), and the results from the current study suggest that there are additional tissue-level effects related to the harvesting and/or morphology of MSTCs that are yet to be fully understood. Deciphering the underlying mechanism(s) governing this morphology dependency of the ability to preserve normal dermal architecture could be a critical step toward engineering physiologically normal full-thickness skin tissue.…”